Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle.

BACKGROUND: The significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics. METHODS: The present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control. RESULTS: The estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB. CONCLUSION: Genomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.

Exploration of the epidemiological consequences of resistance to gastro-intestinal parasitism and grazing management of sheep through a mathematical model.

Predicting the impacts of selection for decreased faecal egg count (FEC) (i.e. host resistance) in grazing ruminants is difficult, due to complex interactions between parasite epidemiology, management and host responses. A mathematical model including heritable between lamb variation in host-parasite interactions, Teladorsagia circumcincta epidemiology and anthelmintic drenching, was developed and used to (i) address such interactions and their impact on outcomes including FEC, live weight (LW, kg) and pasture larval contamination (PC, larvae/kg DM), and (ii) investigate how grazing management strategies, aimed at reducing host exposure to infective larvae via pasture moves at 40 day intervals, affect these outcomes. A population of 10,000 lambs was simulated and resultant FEC predictions used to assign the 1,000 lambs with the highest and lowest predicted FEC to 'susceptible' (S) and 'resistant', (R) groups, respectively. The predicted average FEC of the S group was ∼8.5-fold higher than the R group across a grazing season. The R and S groups were then simulated to graze separate pastures (R(sep) and S(sep)); and repeated for 3 grazing seasons to allow predictions to diverge and stabilize. Further, different grazing strategies were superimposed on all groups. PC and average FEC were affected by whether lambs of different resistance genotype grazed together or separately, with differences increasing across grazing seasons. By the third grazing season the average PC of the R(sep) group was reduced by ∼83%, and the S(sep) group was increased by ∼240%, in comparison to the whole population average. Average FEC of the R(sep) group was reduced by ∼40%, and the S(sep) group increased by ∼46% in comparison to the R and S groups, respectively, whilst drenching had little impact on the proportional differences in FEC between groups. Predicted LW was similar for the R and R(sep) groups irrespective of anthelmintic treatment, whilst LW of the S(sep) group was reduced by ∼14% compared to the S group for un-drenched lambs, and by ∼4% for drenched lambs. The differing grazing strategies were predicted to have little impact on FEC or LW, with the exception of the S(sep) group which was predicted to have a 2 kg increase in LW when drenched and moved to a clean pasture. Together, these results suggest that host genotype has a substantial impact on parasite epidemiology, however the benefits of anthelmintic treatment and grazing management should only be expected for susceptible animals. This supports the use of targeted selective treatment, focussing on susceptible animals.

Exploring the assumptions underlying genetic variation in host nematode resistance (Open Access publication).

The wide range of genetic parameter estimates for production traits and nematode resistance in sheep obtained from field studies gives rise to much speculation. Using a mathematical model describing host - parasite interactions in a genetically heterogeneous lamb population, we investigated the consequence of: (i) genetic relationships between underlying growth and immunological traits on estimated genetic parameters for performance and nematode resistance, and (ii) alterations in resource allocation on these parameter estimates. Altering genetic correlations between underlying growth and immunological traits had large impacts on estimated genetic parameters for production and resistance traits. Extreme parameter values observed from field studies could only be reproduced by assuming genetic relationships between the underlying input traits. Altering preferences in the resource allocation had less pronounced effects on the genetic parameters for the same traits. Effects were stronger when allocation shifted towards growth, in which case worm burden and faecal egg counts increased and genetic correlations between these resistance traits and body weight became stronger. Our study has implications for the biological interpretation of field data, and for the prediction of selection response from breeding for nematode resistance. It demonstrates the profound impact that moderate levels of pleiotropy and linkage may have on observed genetic parameters, and hence on outcomes of selection for nematode resistance.