S. C. Bishop

How hosts control worms

Nematodes are a major cause of disease and death in humans, domestic animals and wildlife. Understanding why some individuals suffer severely whereas others exposed to the same infection remain healthy may assist in the development of rational and sustainable strategies to control infection. Here, using a quantitative genetic analysis of the parasitic nematode population that had accumulated naturally in lambs, we find no apparent influence of host genetics on nematode numbers but an extremely strong influence on average worm length and fecundity. Our results indicate that in growing lambs the main manifestation of genetic resistance is the control of worm fecundity.

Mechanisms underlying resistance to nematode infection

Lambs show considerable genetic variation in faecal egg count following natural, predominantly Ostertagia circumcinta infection. This genetic variation is acquired and not innate. Worm length is positively associated with worm fecundity. The genetic variation in faecal egg count is a consequence of genetic variation in worm length and hence worm fecundity, and not of genetic variation in worm burdens. In contrast to lambs, mature sheep may be able to regulate both fecundity and worm numbers. In lambs, three factors account for the majority of the variation in worm length: the strength of the local IgA response against fourth-stage larvae, the specificity of this response against four molecules in particular, and the density-dependent influence of worm number.

The susceptibility of Atlantic salmon fry to freshwater infectious pancreatic necrosis is largely explained by a major QTL

Infectious pancreatic necrosis (IPN) is a viral disease with a significant negative impact on the global aquaculture of Atlantic salmon. IPN outbreaks can occur during specific windows of both the freshwater and seawater stages of the salmon life cycle. Previous research has shown that a proportion of the variation seen in resistance to IPN is because of host genetics, and we have shown that major quantitative trait loci (QTL) affect IPN resistance at the seawater stage of production. In the current study, we completed a large freshwater IPN challenge experiment to allow us to undertake a thorough investigation of the genetic basis of resistance to IPN in salmon fry, with a focus on previously identified QTL regions. The heritability of freshwater IPN resistance was estimated to be 0.26 on the observed scale and 0.55 on the underlying scale. Our results suggest that a single QTL on linkage group 21 explains almost all the genetic variation in IPN mortality under our experimental conditions. A striking contrast in mortality is seen between fry classified as homozygous susceptible versus homozygous resistant, with QTL-resistant fish showing virtually complete resistance to IPN mortality. The findings highlight the importance of the major QTL in the genetic regulation of IPN resistance across distinct physiological lifecycle stages, environmental conditions and viral isolates. These results have clear scientific and practical implications for the control of IPN.

Modeling of host genetics and resistance to infectious diseases: understanding and controlling nematode infections

This paper considers approaches to modeling the dynamics of infectious disease and the application of such models to nematode parasite infections in ruminants. Particularly, these models are developed to account for host genetics and may be used to assess the effects of using genetics to control nematode infections. Three main issues are critically examined: the infection transmission cycle from pasture to host to pasture, the expected genetic relationships between resistance and performance, and the risks of parasite evolution in response to genetic changes in the host. To obtain answers that are realistic and of practical use, the modeling approaches require a solid grounding in biology. This biology is formalized and described using mathematical techniques, with the models parameterized using experimental or field data. Transmission dynamics have been quantified by modeling and are backed by strong experimental data. Selection for resistance will be successful in reducing egg output, pasture larval contamination and hence subsequent larval challenge. Modeling frameworks have been developed to predict genetic relationships between resistance to infectious disease and performance in general, and genetic correlations predicted for nematode resistance are close to mean published values. These predicted correlations strengthen as the larval challenge increases and the dietary (protein) adequacy decreases, however modeling challenges remain. Lastly, although convincing experimental data is not yet available, arguments based on modeling suggest that the risks of parasite evolution in response to genetic changes in the host should be less than the risks arising from other control strategies, such as anthelmintics. Thus, modeling techniques predict that selective breeding for resistance should be an effective and sustainable complementary control measure.

The genetic basis of resistance to Ostertagia circumcincta in lambs

The relationship between Ostertagia (Teladorsagia) circumcincta and sheep is one of the best understood host-parasite relationships in any species. The key components of resistance have been quantified, the extent of genetic control has been established for lambs, and methods now exist to breed lambs which will be both more resistant to worms and more productive than unselected lambs. A major gene for resistance has been identified within or around the major histocompatibility complex, and this gene appears to be the strongest yet identified for resistance to any parasite species. The most important mechanisms of resistance are local IgA responses which regulate worm fecundity and immediate hypersensitivity responses which regulate worm burdens. IgA responses develop before effective immediate hypersensitivity responses. Good simulation models now exist to predict, for example, outbreaks of disease and the response of sheep to selection. The challenge now is to use our improved understanding of the population biology to develop even better simulation models and to produce expert systems based on these models which can be used by veterinarians and others to determine optimal procedures for individual farms to control disease and reduce sub-clinical economic losses.

The repeatability of faecal egg counts, peripheral eosinophil counts, and plasma pepsinogen concentrations during deliberate infections with Ostertagia circumcincta

Faecal egg counts, peripheral blood eosinophil counts and plasma pepsinogen concentrations were monitored during 2 successive, deliberate infections in 24 Scottish Blackface sheep. For all 3 techniques, the repeatability of replicate counts or of measurements made at short intervals were high which suggests that all 3 assays were reliable. Within an infection the repeatability of different samples from the same animal decreased as the interval between samples increased. The repeatability between infections was only moderate for faecal egg counts but high for peripheral eosinophil counts and plasma pepsinogen concentrations. Of the 3 variables, faecal egg count was the most strongly associated with the worm burden. Together, the three variables accounted for, in a statistical sense, one half of the variation in worm burden. The three variables, if measured concurrently, should provide a more effective identification of resistant and susceptible lambs.

Multi-trait selection indexes for sustainable UK hill sheep production

Three selection indexes for the UK hill sheep sector are derived to suit the extremes of hill production systems. These are: (i) intensive, where all surplus lambs not required for breeding are finished for slaughter, (ii) extensive, where all surplus ‘store’ lambs are sold to other farmers for finishing, and (iii) semi-intensive, which is intermediate between the two extremes, i.e. farms finish some lambs for slaughter and sell others as store lambs. Parameters for 12 breeding goal and index traits were estimated using a total of 3962 lamb records and 5944 ewe lambing records from Scottish Blackface sheep on two Scottish Agricultural College experimental hill farms. The breeding goal comprised carcass, maternal and survival traits. The evaluation of these indexes showed that improvements in maternal traits are possible, along with more modest improvements in carcass quality traits. Responses to selection are expected to be lower for the extensive farm in general, compared with the intensive farm. Evaluations of alternative indexes show that an index using measurements of fat and muscle on ewes rather than on lambs may be more cost-effective to implement in practice, compared with the original index, although this change results in a higher (i.e. undesirable) gain in mature size. Sensitivity analyses showed that in general, the indexes are robust to changes in economic values and to changes in heritability estimates.

An assessment of opportunities to dissect host genetic variation in resistance to infectious diseases in livestock

This paper reviews the evidence for host genetic variation in resistance to infectious diseases for a wide variety of diseases of economic importance in poultry, cattle, pig, sheep and Atlantic salmon. Further, it develops a method of ranking each disease in terms of its overall impact, and combines this ranking with published evidence for host genetic variation and information on the current state of genomic tools in each host species. The outcome is an overall ranking of the amenability of each disease to genomic studies that dissect host genetic variation in resistance. Six disease-based assessment criteria were defined: industry concern, economic impact, public concern, threat to food safety or zoonotic potential, impact on animal welfare and threat to international trade barriers. For each category, a subjective score was assigned to each disease according to the relative strength of evidence, impact, concern or threat posed by that particular disease, and the scores were summed across categories. Evidence for host genetic variation in resistance was determined from available published data, including breed comparison, heritability studies, quantitative trait loci (QTL) studies, evidence of candidate genes with significant effects, data on pathogen sequence and on host gene expression analyses. In total, 16 poultry diseases, 13 cattle diseases, nine pig diseases, 11 sheep diseases and three Atlantic salmon diseases were assessed. The top-ranking diseases or pathogens, i.e. those most amenable to studies dissecting host genetic variation, were Salmonella in poultry, bovine mastitis, Mareks disease and coccidiosis, both in poultry. The top-ranking diseases or pathogens in pigs, sheep and Atlantic salmon were Escherichia coli, mastitis and infectious pancreatic necrosis, respectively. These rankings summarise the current state of knowledge for each disease and broadly, although not entirely, reflect current international research efforts. They will alter as more information becomes available and as genome tools become more sophisticated for each species. It is suggested that this approach could be used to rank diseases from other perspectives as well, e.g. in terms of disease control strategies.

An ovine lymphocyte antigen is associated with reduced faecal egg counts in four-month-old lambs following natural, predominantly Ostertagia circumcincta infection

Ovine lymphocyte antigen is associated with reduced faecal egg counts in 4-month-old lambs following natural, predominantly Ostertagia circumcincta infection. International Journal for Parasitology 26: 423-428. Ten lymphocyte antigens were defined in a flock of Scottish Blackface sheep known to be naturally exposed to infection with Ostertagia circumcincta. Population and family studies suggested that the 10 antigens were products of class I loci. Antigen G13br was in linkage disequilibrium with allele g2 at the DRB1 locus. The g2 allele has previously been associated with reduced faecal egg counts in a different crop of lambs from the same farm. In this study antigen G13br was also associated with a reduction in faecal egg counts. The results provide partial confirmation of the role of the major histocompatibility complex in resistance to natural, predominantly O. circumcincta infection.

Genetic control of resistance to gastro-intestinal parasites in crossbred cashmere-producing goats: responses to selection, genetic parameters and relationships with production traits

This paper investigates the genetic control of the resistance of goats to nematode parasites, and relationships between resistance and production traits. The data set comprised faecal egg counts (FECs) measured on 830 naturally challenged (predominant species Teladorsagia circumcincta ), crossbred cashmere-producing goats over 5 years (1993-1997) and production traits (fibre traits and live weight) on 3100 goats from the same population in Scotland, over 11 years (1987-1997). Egg counts comprised repeated measurements (4 to 11) taken at 12 to 18 months of age and production traits, i.e. live weight and fibre traits, were measured at approximately 5 months of age. The goats for which FECs were available were subdivided into a line selected for decreased FECs, using the geometric mean FEC across the measurement period and goats not selected on the basis of FECs, acting as controls. The selected line had significantly lower FECs, compared with the control, in 4 out of 5 years (back transformed average proportional difference of 0·23). The heritability of a single FEC measurement (after cubic root transformation) was 0·17 and the heritability of the mean FEC was 0·32. The heritabilities of the fibre traits were moderate to high with the majority in excess of 0·5. The heritability of live weight was 0·22. Genetic correlations between FECs and production traits were slightly positive but not significantly different from zero. Phenotypic and environmental correlations were very close to zero with the environmental correlations always being negative. It is concluded that selection for reduced FEC is possible for goats. Benefits of such selection will be seen when animals are kept for more than 1 year of productive life.