Background Selection of cattle that are less sensitive to environmental variation in unfavorable environments and more adapted to harsh conditions is of primary importance for tropical beef cattle production systems. Understanding the genetic background of sensitivity to environmental variation is necessary for developing strategies and tools to increase efficiency and sustainability of beef production. We evaluated the degree of sensitivity of beef cattle performance to environmental variation, at the animal and molecular marker levels (412 K single nucleotide polymorphisms), by fitting and comparing the results of different reaction norm models (RNM), using a comprehensive dataset of Nellore cattle raised under diverse environmental conditions. Results Heteroscedastic RNM (with different residual variances for environmental level) provided better fit than homoscedastic RNM. In addition, spline and quadratic RNM outperformed linear RNM, which suggests the existence of a nonlinear genetic component affecting the performance of Nellore cattle. This nonlinearity indicates that within-animal sensitivity depends on the environmental gradient (EG) level and that animals may present different patterns of sensitivity according to the range of environmental variations. The spline RNM showed that sensitivity to environmental variation from harsh to average EG is lowly correlated with sensitivity from average to good EG, at both the animal and molecular marker levels. Although the genomic regions that affect sensitivity in harsher environments were not the same as those associated with less challenging environments, the candidate genes within those regions participate in common biological processes such as those related to inflammatory and immune response. Some plausible candidate genes were identified. Conclusions Sensitivity of tropical beef cattle to environmental variation is not continuous along the environmental gradient, which implies that animals that are less sensitive to harsher conditions are not necessarily less responsive to variations in better environmental conditions, and vice versa. The same pattern was observed at the molecular marker level, i.e. genomic regions and, consequently, candidate genes associated with sensitivity to harsh conditions were not the same as those associated with sensitivity to less challenging conditions. Electronic supplementary material The online version of this article (10.1186/s12711-019-0470-x) contains supplementary material, which is available to authorized users.
Relative survival and excess mortality approaches are commonly used to estimate and compare net survival from cancer. These approaches are based on the assumption that the underlying (non-cancer) mortality rate of cancer patients is the same as that of the general population. This assumption is likely to be violated particularly in the context of smoking-related cancers. The magnitude of this bias has not been estimated. The objective of this article is to estimate the bias in relative survival ratios (RSRs) and excess mortality rate ratios (EMRRs) from using total population compared to correct subpopulation specific life-tables. Analyses were conducted on 1996-2001 linked census-cancer data (including smoking status) for people with lung and bladder cancer, using sex-specific (standard practice), sex-and ethnic-specific, sex-and smoking-specific and sex-, ethnic-and smoking-specific life-tables. Five-year RSRs using sex-specific life-tables, compared to fully stratified lifetables, were underestimated by 10-25% for current smoking and Maori populations. For example, the current smoker male bladder cancer RSR was 0.700 for sex-specific life-tables, compared to 0.838 for fully stratified life-tables. Similarly, EMRRs comparing current to never smokers and Maori to non-Maori were overestimated using sex-specific life-tables only: modestly only for lung cancer, but markedly for bladder cancer. For example, the EMRR comparing current to never smokers with bladder cancer in a fully adjusted regression model was 1.475 when using sex-specific life-tables only, but reduced to 1.098 when using fully stratified life-tables. Substantial bias can occur when estimating relative cancer survival across subpopulations if non-matching life-tables are used.Relative survival and excess mortality analyses are commonly used to estimate and compare net survival (or excess mortality) among patients with cancer. Relative survival and excess mortality analyses use overall survival and the total number of deaths, respectively, and then adjust for the expected survival and number of deaths using population life-tables. Relative survival ratios (RSRs) are calculated using the ratio of observed survival among cancer patients to the expected survival in the underlying population. Excess mortality rate modelling is a mirror image of survival analyses and usually undertaken with a Poisson model using the observed minus expected number of deaths as the dependent variable. 1-3The key advantages of relative survival and excess mortality rate methods are that error due to incorrect coding of cause of death is avoided, and that one captures cancerconsequent deaths through the difference in observed and expected deaths (or survival).2 The key disadvantage, however, is that one has to assume that the population lifetables provide accurate estimates of the expected mortality rate or survival for the people developing cancer. In other words, these methods assume that those who develop cancer would have had the same risk of mortality as the general pop...
Background: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. Results: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. Conclusions: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species.
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