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, 7 (3), e33526

Quantitative Trait Loci Associated With the Immune Response to a Bovine Respiratory Syncytial Virus Vaccine

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Quantitative Trait Loci Associated With the Immune Response to a Bovine Respiratory Syncytial Virus Vaccine

Richard J Leach et al. PLoS One.

Abstract

Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected.Heifers from the same population (n = 195) were subsequently immunised with a 40-mer Foot-and-Mouth Disease Virus peptide (FMDV) in a previous publication. Several of these QTL associated with the FMDV traits had overlapping peak positions with QTL in the current study, including the QTL on BTA23 which included the bovine Major Histocompatibility Complex (BoLA), and QTL on BTA9 and BTA24, suggesting that the genes underlying these QTL may control responses to multiple antigens. These results lay the groundwork for future investigations to identify the genes underlying the variation in clearance of maternal antibody and response to vaccination.

Conflict of interest statement

Competing Interests: The authors have the following interest: Pfizer Animal Health provided a proportion of the funding for this investigation. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. BTA 17: Significant QTL.
F-statistic profiles for the total IgG and IgG1 response elicited by the BRSV vaccine two weeks post vaccination. The dashed horizontal line represents the threshold of the 1% chromosome wide significance level (F = 6.26) and the constant horizontal line represents the threshold of the 1% chromosomal wide significance level (F = 8.16).
Figure 2
Figure 2. BTA 8: Significant QTL.
F-statistic profiles for the total IgG and IgG1 responses elicited by the BRSV vaccine seven weeks post vaccination and using the AUC measurement. All the QTL are above the 5% chromosome wide significance level.
Figure 3
Figure 3. BTA 14: Significant QTL.
F-statistic profiles for the IgG2 response elicited by the BRSV vaccine two and seven weeks post vaccination and using the AUC measurement. The constant horizontal line represents the threshold of the 1% chromosomal wide significance level (F = 6.43).
Figure 4
Figure 4. BTA 23: Significant QTL.
F-statistic profiles for the IgG2 response elicited by the BRSV vaccine two weeks post vaccination (peak, 31; F-statistic 6.82) and the AUC measurement (peak, 27; F-statistic, 4.97) and for the IgG1 (peak, 39; F-statistic, 4.16) and IgG2 (peak, 33; F-statistic, 4.08) levels elicited by the FMDV peptide 2 and 10 weeks post immunisation, respectively.

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