Predicted effect of ‘22’ genotype on second avian (<i>a2</i>, red) and second bovine (<i>b2</i>, black) measurements.

<p>The predicted impact of the ‘22’ parameter (0 = not ‘22’, 1 = ‘22’) on the second avian and second bovine swelling size measurements within our study population is summarised as a ‘beanplot’. The solid envelope represents the smoothed density kernel for the predicted values. Actual values are over-plotted as solid lines and the vertical dotted lines indicate the mean effect sizes across all breeds for the two measurements. Predicted values are calculated from the two Poisson regression models: <i>a2</i> ∼ p22 + breed + age; <i>b2</i> ∼ p22 + breed+age (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058245#pone.0058245.s002" target="_blank">Tables S2</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058245#pone.0058245.s003" target="_blank">S3</a>).</p

Genetic Predisposition to Pass the Standard SICCT Test for Bovine Tuberculosis in British Cattle

<div><p>Bovine tuberculosis (bTB) imposes an important financial burden on the British cattle industry, yet despite intense efforts to control its spread, incidence is currently rising. Surveillance for bTB is based on a skin test that measures an immunological response to tuberculin. Cattle that fail the test are classified as “reactors” and slaughtered. Recent studies have identified genetic markers associated with the reaction of cattle to the tuberculin test. At marker INRA111 a relatively common ‘22’ genotype occurs significantly more frequently in non-reactor cattle. Here we test the possibility that the putative protective ‘22’ genotype does not confer resistance but instead causes cattle that carry it to react less strongly to the prescribed test, and hence avoid slaughter, potentially even though they are infected. We show that, after controlling for age and breed, ‘22’ cattle react less strongly to the immunological challenge and may therefore be less likely to be classified as a reactor. These results highlight the potential discrepancy between infection and test status and imply that the effectiveness of the test-and-slaughter policy may be being compromised by selection for cattle that are genetically predisposed to react less strongly to tuberculin.</p> </div

Prediction of difference in swelling size between initial and final measurements at the avian tuberculin injection site (<i>da</i>) by ‘22’ genotype.

<p>Incident risk and odds ratios for both components of a zero-inflated Poisson model fitted to the avian difference (<i>da</i> ∼ Age + <i>a1</i> + p22). Odds and incident risk ratios (from the Poisson count model and binomial zero inflation terms respectively) are presented to two significant figures, along with 95% confidence intervals calculated from 10000 parametric bootstraps. Significant effects at the 95% level are highlighted in bold. While the age co-efficient is highly significant with the Poisson portion of the model, the p22 effect is only marginally significant for <i>da</i>. The marginal significance of the p22 effect is further emphasised by the variability in the bootstrapped confidence interval, which constitutes a more conservative test.</p

Sample set used in the current study.

<p>These represent 625 animals and 22 breeds drawn from an original set of 1810 samples collected. Qualifications for inclusion are: being genotyped for marker INRA111, having passed their first SICCT test, being recorded in the VeBus database and having at least four other samples from the same breed. The Table lists, for each of these breeds, the abbreviated code, the full breed name and the numbers of non-reactors (NR) and reactors (R), partitioned by whether they derived from the original (O-) Driscoll et al. study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058245#pone.0058245-Driscoll1" target="_blank">[14]</a> (n = 141) or are new (N-) samples (n = 385).</p

Test and animal factors associated with probability of being the ‘22’ genotype.

<p>Estimated parameters from the final selected logistic regression model for the probability of an animal possessing the ‘22’ genotype (p22 ∼ Age + <i>a2</i> + breed). Odds ratios are presented to two significant figures, along with 95% confidence intervals. Significant effects at the 95% level are highlighted in bold. The selected model shows no significant evidence of a lack of fit (p-value = 0.51). Predictive ability of the selected models was assessed using the receiver-operating-characteristic (ROC) curve, which has an area under the curve of 0.68. Breed effects are measured relative to the Holstein Breed (HOL) that is the most represented breed within the study population. For breed codes, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058245#pone-0058245-t001" target="_blank">Table 1</a>.</p

Predicted effect of ‘22’ genotype on the swelling induced by avian and bovine tuberculin challenges.

<p>Swelling size is taken as the difference between the initial measurement, taken immediately following injection, and the final measurement, taken after the prescribed 72 hour time delay that allows an immune response to occur (hereafter = ‘difference’). This controls for skin thickness differences between animals. The graphs show the predicted impact of the ‘22’ parameter (0 = not ‘22’, 1 = ‘22’) on the avian (da, left) and bovine (<i>db</i>, right) differences. Predicted values are calculated from the respective zero-inflated regression models <i>da</i> ∼ age + <i>a</i>1 + p22, <i>db</i> ∼ age + <i>b1</i> + p22 described within the main text (summarised in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058245#pone-0058245-t003" target="_blank">Tables 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058245#pone-0058245-t004" target="_blank">4</a>). The distribution of predicted values with (solid line) and without (dashed line) the ‘22’ genotype are compared as smoothed density curves. No effect was found for the bovine differences but the model predicts a smaller avian difference (<i>da</i>) when among animals with the ‘22’ genotype.</p

Prediction of difference in swelling size between initial and final measurements at the bovine tuberculin injection site (<i>db</i>) by ‘22’ genotype.

<p>Incident risk and odds ratios for both components of a zero-inflated Poisson model fitted to the bovine difference (<i>db</i> ∼ Age + <i>b1</i> + p22). Odds and incident risk ratios (from the Poisson count model and binomial zero inflation terms respectively) are presented to two significant figures, along with 95% confidence intervals calculated from 10000 parametric bootstraps. Significant effects at the 95% level are highlighted in bold. While the age co-efficient is highly significant with the Poisson portion of the model, the p22 effect is only marginally significant for <i>da</i>. The marginal significance of the p22 effect is further emphasised by the variability in the bootstrapped confidence interval, which constitutes a more conservative test.</p