Abstract

BackgroundThe increasing prevalence of bovine tuberculosis (bTB) in the UK and the limitations of the currently available diagnostic and control methods require the development of complementary approaches to assist in the sustainable control of the disease. One potential approach is the identification of animals that are genetically more resistant to bTB, to enable breeding of animals with enhanced resistance. This paper focuses on prediction of resistance to bTB. We explore estimation of direct genomic estimated breeding values (DGVs) for bTB resistance in UK dairy cattle, using dense SNP chip data, and test these genomic predictions for situations when disease phenotypes are not available on selection candidates.Methodology/Principal FindingsWe estimated DGVs using genomic best linear unbiased prediction methodology, and assessed their predictive accuracies with a cross validation procedure and receiver operator characteristic (ROC) curves. Furthermore, these results were compared with theoretical expectations for prediction accuracy and area-under-the-ROC-curve (AUC). The dataset comprised 1151 Holstein-Friesian cows (bTB cases or controls). All individuals (592 cases and 559 controls) were genotyped for 727,252 loci (Illumina Bead Chip). The estimated observed heritability of bTB resistance was 0.23±0.06 (0.34 on the liability scale) and five-fold cross validation, replicated six times, provided a prediction accuracy of 0.33 (95% C.I.: 0.26, 0.40). ROC curves, and the resulting AUC, gave a probability of 0.58, averaged across six replicates, of correctly classifying cows as diseased or as healthy based on SNP chip genotype alone using these data.Conclusions/SignificanceThese results provide a first step in the investigation of the potential feasibility of genomic selection for bTB resistance using SNP data. Specifically, they demonstrate that genomic selection is possible, even in populations with no pedigree data and on animals lacking bTB phenotypes. However, a larger training population will be required to improve prediction accuracies.

Highlights

  • Bovine tuberculosis is caused by Mycobacterium bovis, an aerobic Gram+ bacillus and member of the M. tuberculosis complex

  • genomic BLUP (GBLUP) and Cross Validation The GBLUP analysis gave an estimate for the heritability of bovine tuberculosis (bTB) susceptibility of 0.2360.06 on the observed scale for the full data set, 0.2360.07 for the dataset after removing the 40 individuals identified as a distinct sub-population from the Principal component analysis (PCA) and 0.2160.07 for the reduced data set with the Friesian individuals excluded

  • For each of the cross validation folds and across the six replications, both for the full and the dataset without the Friesians, the observed phenotypes were regressed on the predicted direct genomic estimated breeding values (DGVs) (Table 3, detailed tables can be found in the Supplementary Material, Tables S4, S5 in file S1)

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Summary

Introduction

Bovine tuberculosis (bTB) is caused by Mycobacterium bovis, an aerobic Gram+ bacillus and member of the M. tuberculosis complex. Bovine tuberculosis eradication in the UK is impaired by limitations of the available diagnostic and control methods. Vaccination using Bacillus Calmette Guerin (BCG) is precluded because vaccinated animals would currently be indistinguishable from infected animals using standard tuberculin tests [3]. The increasing prevalence of bovine tuberculosis (bTB) in the UK and the limitations of the currently available diagnostic and control methods require the development of complementary approaches to assist in the sustainable control of the disease. We explore estimation of direct genomic estimated breeding values (DGVs) for bTB resistance in UK dairy cattle, using dense SNP chip data, and test these genomic predictions for situations when disease phenotypes are not available on selection candidates

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