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      Evidence for genetic variance in resistance to tuberculosis in Great Britain and Irish Holstein-Friesian populations

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          Abstract

          Background

          Here, we jointly summarise scientific evidence for genetic variation in resistance to infection with Mycobacterium bovis, the primary agent of bovine tuberculosis ( TB), provided by two recent and separate studies of Holstein-Friesian dairy cow populations in Great Britain ( GB) and Ireland.

          Methods

          The studies quantified genetic variation within archived data from field and abattoir surveillance control programmes within each country. These data included results from the single intradermal comparative tuberculin test ( SICTT), abattoir inspection for TB lesions and laboratory confirmation of disease status. Threshold animal models were used to estimate variance components for responsiveness to the SICTT and abattoir confirmed M. bovis infection. The link functions between the observed 0/1 scale and the liability scale were the complementary log-log in the GB, and logit link function in the Irish population.

          Results and discussion

          The estimated heritability of susceptibility to TB, as judged by responsiveness to the SICTT, was 0.16 (0.012) and 0.14 (0.025) in the GB and Irish populations, respectively. For abattoir or laboratory confirmation of infection, estimates were 0.18 (0.044) and 0.18 (0.041) from the GB and the Irish populations, respectively.

          Conclusions

          Estimates were all significantly different from zero and indicate that exploitable variation exists among GB and Irish Holstein Friesian dairy cows for resistance to TB. Epidemiological analysis suggests that factors such as variation in exposure or imperfect sensitivity and specificity would have resulted in underestimation of the true values.

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          Most cited references7

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          On the Genetic Interpretation of Disease Data

          Background The understanding of host genetic variation in disease resistance increasingly requires the use of field data to obtain sufficient numbers of phenotypes. We introduce concepts necessary for a genetic interpretation of field disease data, for diseases caused by microparasites such as bacteria or viruses. Our focus is on variance component estimation and we introduce epidemiological concepts to quantitative genetics. Methodology/Principal Findings We have derived simple deterministic formulae to predict the impacts of incomplete exposure to infection, or imperfect diagnostic test sensitivity and specificity on heritabilities for disease resistance. We show that these factors all reduce the estimable heritabilities. The impacts of incomplete exposure depend on disease prevalence but are relatively linear with the exposure probability. For prevalences less than 0.5, imperfect diagnostic test sensitivity results in a small underestimation of heritability, whereas imperfect specificity leads to a much greater underestimation, with the impact increasing as prevalence declines. These impacts are reversed for prevalences greater than 0.5. Incomplete data recording in which infected or diseased individuals are not observed, e.g. data recording for too short a period, has impacts analogous to imperfect sensitivity. Conclusions/Significance These results help to explain the often low disease resistance heritabilities observed under field conditions. They also demonstrate that incomplete exposure to infection, or suboptimal diagnoses, are not fatal flaws for demonstrating host genetic differences in resistance, they merely reduce the power of datasets. Lastly, they provide a tool for inferring the true extent of genetic variation in disease resistance given knowledge of the disease biology.
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            Evidence of genetic resistance of cattle to infection with Mycobacterium bovis.

            Anecdotal evidence points to genetic variation in resistance of cattle to infection with Mycobacterium bovis, the causative agent of bovine tuberculosis (BTB), and published experimental evidence in deer and cattle suggests significant genetic variation in resistance and reactivity to diagnostic tests. However, such genetic variation has not been properly quantified in the United Kingdom dairy cattle population; it is possible that it exists and may be a factor influencing the occurrence of BTB. Using models based on the outcome of the process of diagnosis (ultimate fate models) and on the outcome of a single stage of diagnosis (continuation ratio models, herd test-date models), this study shows that there is heritable variation in individual cow susceptibility to BTB, and that selection for milk yield is unlikely to have contributed to the current epidemic. Results demonstrate that genetics could play an important role in controlling BTB by reducing both the incidence and the severity of herd breakdowns.
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              Genetics of tuberculosis in Irish Holstein-Friesian dairy herds.

              Information is lacking on genetic parameters for tuberculosis (TB) susceptibility in dairy cattle. Mycobacterium bovis is the principal agent of tuberculosis in cattle. The objective of this study was to quantify the genetic variation present among Irish Holstein-Friesian dairy herds in their susceptibility to M. bovis infection. A total of 15,182 cow and 8,104 heifer single intradermal comparative tuberculin test (SICTT, a test for M. bovis exposure and presumed infection) records from November 1, 2002, to October 31, 2005, were available for inclusion in the analysis. Data on observed carcass TB lesions from abattoirs were also available for inclusion in the analysis. The only animals retained were those present in a herd during episodes in which at least 2 animals showed evidence of infection; this ensured a high likelihood of exposure to M. bovis. Linear animal models, and sire and animal threshold models were used to estimate the variance components for susceptibility to M. bovis-purified protein derivative (PPD) responsiveness and confirmed M. bovis infection. The heritability estimates from the threshold sire models were biased upward because the relatedness between dam-daughter pairs was ignored. The threshold animal model produced heritability estimates of 0.14 in cows and 0.12 in heifers for susceptibility to M. bovis-PPD responsiveness, and 0.18 in cows for confirmed M. bovis infection susceptibility. Therefore, exploitable genetic variation exists among Irish dairy cows for susceptibility to M. bovis infection. Sire rankings from the linear and threshold animal models were similar, indicating that either model could be used for the analysis of susceptibility to M. bovis-PPD responsiveness. A favorable genetic correlation close to unity was observed between susceptibility to confirmed M. bovis infection and M. bovis-PPD responsiveness, indicating that direct selection for resistance to M. bovis-PPD responsiveness will indirectly reduce susceptibility to confirmed M. bovis infection. Data from the national TB eradication program could be used routinely to estimate breeding values for susceptibility to M. bovis infection.
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                Author and article information

                Conference
                BMC Proc
                BMC Proceedings
                BioMed Central
                1753-6561
                2011
                3 June 2011
                : 5
                : Suppl 4
                : S15
                Affiliations
                [1 ]The Roslin Institute, Roslin Biocentre, Roslin, Midlothian EH25 9RG, UK
                [2 ]Institute of Evolutionary Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
                [3 ]Moorepark Production Research Centre, Fermoy, Co. Cork, Ireland
                [4 ]Centre for Veterinary Epidemiology and Risk Analysis, UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland
                [5 ]Department of Agriculture, Fisheries and Food, Kildare St., Dublin 2, Ireland
                [6 ]The Irish Cattle Breeding Federation, Bandon, Co. Cork, Ireland
                [7 ]Scottish Agricultural College, Bush Estate, Penicuik, Midlothian EH26 0PH, UK
                [8 ]Veterinary Laboratories Agency-Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK
                Article
                1753-6561-5-S4-S15
                10.1186/1753-6561-5-S4-S15
                3108209
                21645294
                743aec4e-5dde-40c0-83d1-af201e8bae5c
                Copyright ©2011 Bermingham et al; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                International Symposium on Animal Genomics for Animal Health (AGAH 2010)
                Paris, France
                31 May - 2 June 2010
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                Medicine
                Medicine

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