Allele/haplotype variation in the MHC-DQA2 gene in Spanish sheep and its association with footrot susceptibility.

Footrot is a contagious disease that affects the hoof of sheep and other ungulates. The severity of the disease varies from a slight limp to the death of the individual due to injuries that prevent them from feeding. Variants of the Major Histocompatibility Complex (MHC)-DQA2 gene (MHC-DQA2) have been associated with a greater or lesser susceptibility to footrot in Greek, New Zealand and German sheep. In this study, variation in ovine MHC-DQA2, the absence or presence of footrot and the severity of infection was analysed in 117 Spanish Merino, Black Merino and Churra Lebrijana sheep. A total of 21 alleles/haplotypes and 65 genotypes were found with different frequencies in these breeds. As found in other studies, the MHC-DQA2 allele *1101 appeared to be associated with increased susceptibility to footrot, while allele *1201 appeared to be associated with decreased susceptibility. Overall this would suggest the ovine MHC plays a role in controlling susceptibility to footrot infection and that there are breed differences in susceptibility. Sheep might therefore be able to be selected by their MHC-DQA2 alleles/haplotypes to reduce the incidence of the disease in flocks.

A genome-wide significant association on chromosome 2 for footrot resistance/susceptibility in Swiss White Alpine sheep.

Footrot is one of the most important causes of lameness in global sheep populations and is characterized by a bacterial infection of the interdigital skin. As a multifactorial disease, its clinical representation depends not only on pathogen factors and environmental components but also on the individual resistance/susceptibility of the host. A genetic component has been shown in previous studies; however, so far no causative genetic variant influencing the risk of developing footrot has been identified. In this study, we genotyped 373 Swiss White Alpine sheep, using the ovine high-density 600k SNP chip, in order to run a DNA-based comparison of individuals with known clinical footrot status. We performed a case-control genome-wide association study, which revealed a genome-wide significant association for SNP rs418747104 on ovine chromosome 2 at 81.2 Mb. The three best associated SNP markers were located at the MPDZ gene, which codes for the multiple PDZ domain crumbs cell polarity complex component protein, also known as multi-PDZ domain protein 1 (MUPP1). This protein is possibly involved in maintaining the barrier function and integrity of tight junctions. Therefore, we speculate that individuals carrying MPDZ variants may differ in their footrot resistance/susceptibility due to modified horn and interdigital skin integrity. In conclusion, our study reveals that MPDZ might represent a functional candidate gene, and further research is needed to explore its role in footrot affected sheep.

Genetic resistance to infections in sheep.

This paper considers genetic resistance to infectious disease in sheep, with appropriate comparison with goats, and explores how such variation may be used to assist in disease control. Many studies have attempted to quantify the extent to which host animals differ genetically in their resistance to infection or in the disease side-effects of infection, using either recorded animal pedigrees or information from genetic markers to quantify the genetic variation. Across all livestock species, whenever studies are sufficiently well powered, then genetic variation in disease resistance is usually seen and such evidence is presented here for three infections or diseases of importance to sheep, namely mastitis, foot rot and scrapie. A further class of diseases of importance in most small ruminant production systems, gastrointestinal nematode infections, is outside the scope of this review. Existence of genetic variation implies the opportunity, at least in principle, to select animals for increased resistance, with such selection ideally used as part of an integrated control strategy. For each of the diseases under consideration, evidence for genetic variation is presented, the role of selection as an aid to disease control is outlined and possible side effects of selection in terms of effects in performance, effects on resistance to other diseases and potential parasite/pathogen coevolution risks are considered. In all cases, the conclusion is drawn that selection should work and it should be beneficial, with the main challenge being to define cost effective selection protocols that are attractive to sheep farmers.

The interaction of host genetics and disease processes in chronic livestock disease: a simulation model of ovine footrot.

A stochastic, individual-based, simulation model of footrot in a flock of 200 ewes was developed that included flock demography, disease processes, host genetic variation for traits influencing infection and disease processes, and bacterial contamination of the environment. Sensitivity analyses were performed using ANOVA to examine the contribution of unknown parameters to outcome variation. The infection rate and bacterial death rate were the most significant factors determining the observed prevalence of footrot, as well as the heritability of resistance. The dominance of infection parameters in determining outcomes implies that observational data cannot be used to accurately estimate the strength of genetic control of underlying traits describing the infection process, i.e. resistance. Further work will allow us to address the potential for genetic selection to control ovine footrot.

Implications of host genetic variation on the risk and prevalence of infectious diseases transmitted through the environment.

Previous studies have shown that host genetic heterogeneity in the response to infectious challenge can affect the emergence risk and the severity of diseases transmitted through direct contact between individuals. However, there is substantial uncertainty about the degree and direction of influence owing to different definitions of genetic variation, most of which are not in line with the current understanding of the genetic architecture of disease traits. Also, the relevance of previous results for diseases transmitted through environmental sources is unclear. In this article a compartmental genetic-epidemiological model was developed to quantify the impact of host genetic diversity on epidemiological characteristics of diseases transmitted through a contaminated environment. The model was parameterized for footrot in sheep. Genetic variation was defined through continuous distributions with varying shape and degree of dispersion for different disease traits. The model predicts a strong impact of genetic heterogeneity on the disease risk and its progression and severity, as well as on observable host phenotypes, when dispersion in key epidemiological parameters is high. The impact of host variation depends on the disease trait for which variation occurs and on environmental conditions affecting pathogen survival. In particular, compared to homogeneous populations with the same average susceptibility, disease risk and severity are substantially higher in populations containing a large proportion of highly susceptible individuals, and the differences are strongest when environmental contamination is low. The implications of our results for the recording and analysis of disease data and for predicting response to selection are discussed.

Breeding for resistance to footrot--the use of hoof lesion scoring to quantify footrot in sheep.

So that genetic studies can be undertaken on footrot in sheep, it is necessary that a reliable and repeatable method to categorise the phenotype is available. This paper summarises the methods used and results obtained from 1600 hoof lesion scores of 100 mixed-age ewes independently scored twice by two trained operators. Using a 5-pont scale describing the severity of foot lesions, residual correlations were used to assess agreement between scorers and scoring occasions. Data were analysed using both zero-1 and continuous data methods. The average prevalence of any score >0 was 15%, and of scores >1 was 12%. The residual correlation between scorers for SUM_FR was 0.87 and between scoring occasions it was also 0.87, indicating high repeatability or agreement both within and between scorers. No significant differences were detected between scorers or between scoring occasions for any of the traits analysed, or different analytical methods used.

[Selection for disease and epidemic resistance in domestic ruminants and swine by indicator traits, marker and causal genes--a review. Part 2: Special immunogenetics of sheep and goats with particular regard for endoparasitoses, scrapie, foot rot and maedi-visna virus infection]. / Selektion beim domestizierten Wiederkäuer und Schwein auf Krankheits- und Seuchenresistenz mit Hilfe von Indikatormerkmalen, Marker- und Kausalgenen--ein Uberblick. 2. Mitteilung: Spezielle Immungenetik bei Schaf und Ziege unter besonderer Berücksichtigung der Endoparasitosen, Scrapie, Moderhinke und der Maedi-Visna-Virusinfektion.

The introduction of the first part deals with immunogenetic investigations on the field of life-stock. The main chapter is outlined as a tabular overview of current opportunities of the application of indicator traits as well as marker and causal genes in breeding for disease resistance in cattle, sheep, goats and swine. In the discussion of the second part, emphasis was laied on diseases of small ruminants in central and western Europe with special respect of endoparasitoses, scrapie, foot-rot and maedi-visna virus infection. Indicator traits are discussed with respect of their advantages and disadvantages. The rigorous selection on specific traits is connected with an increase of the number of homozygotes. In contrary, pathogens do undergo mutations, thus escaping the host's immune system. Out of this point of view it is advisable, to set on selection very cautiously. The role of technologies of modern immunogenetics is pointed out in respect of constructing disease resistant animals.

PCR-RFLP of outer membrane proteins gene of Dichelobacter nodosus: a new tool in the epidemiology of footrot.

Currently only phenotypic epidemiological markers, serogrouping and virulence testing of Dichelobacter nodosus, are available for investigating footrot outbreaks in small ruminants. These methods have limitations in tracing the source of infection. In this study, a genotypic marker, PCR-RFLP of outer membrane protein gene, was used to characterize D. nodosus. The technique was evaluated in a controlled experiment involving two strains of bacteria. PCR-RFLP was found to be highly specific in differentiating isolates obtained from recipient animals infected with different strains. Subsequently, this technique was used to characterize isolates obtained from field cases of footrot in Nepal. A total of 11 patterns was recognized among 66 Nepalese D. nodosus isolates representing four different serogroups. PCR-RFLP also discriminated isolates with similar phenotypic characteristics. However, all isolates which, phenotypically, were virulent were represented by only two patterns irrespective of their serogroups. It is suggested that PCR-RFLP described here could be a useful epidemiological marker in the study of footrot.

Breeding for disease resistance in Merino sheep in Australia.

Breeding for disease resistance in Merino sheep in Australia has attracted considerable research and development attention. Increased labour costs, the reduced efficacy of common anthelmintics and insecticides, consumer demand for products which are free of chemicals and the poor prognosis of alternative long-term control strategies are all forcing sheep breeders to contemplate the best animal health options available, including selective breeding for resistance. The three major diseases which affect sheep production include gastrointestinal nematode parasites, flystrike (cutaneous myiasis) and footrot. Genetic improvement has been shown to be feasible in all these diseases, possibly with little adverse effect on genetic progress in other production traits. Programmes for resistance to internal parasites to be included in practical breeding programmes are now in progress. This paper deals with the incentives for focusing on the three major diseases in Merino sheep, the potential sources of genetic variation, and the means to exploit these sources of variation. The authors also highlight gains and benefits achieved in experimental selection flocks, and the difficulties and options available for commercial breeders.

Association between alleles of the ovine major histocompatibility complex and resistance to footrot.

Variation in natural resistance to footrot may be genetically derived, implying that genetic markers for resistance may exist and allow selection of superior animals. In this study association between variation within the ovine MHC class II region and resistance to footrot was investigated in two trials. Half-sib progeny were subjected to a field challenge with footrot and their condition subsequently recorded. The animals were then typed at their MHC class II loci to investigate associations between inherited paternal haplotype and footrot status. In the first trial an association between MHC haplotype and footrot status was observed across all animals (P = 0.005), when the self-curing and resistant animals were combined (P = 0.002) and when the self-curing animals were excluded from the analysis (P = 0.001). No association was observed in the second trial, a result attributed to the dry weather conditions which led to poor disease transmission and unreliable disease classification.

Genetic-associated resistance to foot rot in selected Targhee sheep.

Three Targhee rams obtained from the Ohio Agricultural and Experimental Station had been identified as foot rot resistant on the basis of results of challenge exposure. In the first breeding trial, when rams were bred to 20 foot rot-susceptible ewes, the percentages of foot rot-resistant offspring from the 3 foot rot-resistant rams were 68, 82, and 100, compared with 55 and 60 for foot rot-resistant offspring from 2 known foot rot-susceptible rams. In the second year, the foot rot-resistant rams were mated with ewes of unknown foot rot status. The foot rot-resistant status of their lambs was compared with that of range-raised lambs whose parents' foot rot status was unknown. During the first year, challenge exposure to the disease consisted of confinement of the lambs in moist or wet pens with sheep affected with the naturally acquired disease. This protocol was repeated for lambs born during the second-year breeding trial. In addition, the right front foot of each lamb was inoculated with a broth culture of Bacteroides nodosus. During the second year, when data that included infected feet from all lambs were analyzed, 41% of the progeny of the foot rot-resistant rams and 17% of the offspring of parents of unknown foot rot status were unaffected by the disease. When the B nodosus-inoculated foot was not included in the analysis, however, 61% of the progeny of the foot rot-resistant rams and 29% of the others were unaffected. The resistance to foot rot undoubtedly is hereditary. The mechanism of resistance may be in the interdigital skin.(ABSTRACT TRUNCATED AT 250 WORDS)