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

Abstract

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.

An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance

“…(2011) and Amos et al . (2013) achieved the lower statistical significance threshold. The most significant SNP locus on chromosomes BTA9 and BTA11 was rs110974556 on BTA9 with chromosomal position 40 944 275 bp, which is ~36 Mb away from the published microsatellite BMS2753 , but this did not achieve chromosomal significance.…”

“…(2013), and used a case–control population to test published candidate regions and other regions using high‐density SNP data. No evidence was found, neither a SNP effect nor dominance variance, to support the region previously published by Amos et al .…”

“…No evidence was found, neither a SNP effect nor dominance variance, to support the region previously published by Amos et al . (2013), which had been interpreted as showing a heterozygote advantage for resistance. In contrast, the findings of this study suggest that a region on BTA6 (rs43032684) may show dominance variance in bTB resistance, the SNP analysis suggesting a heterozygote disadvantage with heterozygotes more likely to be diseased.…”

“…(2011) and associated with a protective effect against reacting to the bTB diagnostic SICCT test (Amos et al . 2013), namely microsatellites INRA111 (BTA11: 40 311 694–40 311 817 bp) and BMS2753 (BTA9: 76 800 661–76 800 769 bp). Here, the 20 SNPs on each side of the two microsatellites were assessed using a significance threshold of −log 10 (0.05/80) = 3.2.…”

“…A previous publication provided suggestive evidence of over‐dominance protecting heterozygotes from culling as a result of the bTB diagnostic SICCT test (Amos et al . 2013), which would be an important consideration shaping bTB eradication policy if it were confirmed. Therefore, an additional objective was to test these previous findings on a much larger dataset.…”