An explicit immunogenetic model of gastrointestinal nematode infection in sheep

Gastrointestinal nematodes are a global cause of disease and death in humans, wildlife and livestock. Livestock infection has historically been controlled with anthelmintic drugs, but the development of resistance means that alternative controls are needed. The most promising alternatives are vaccination, nutritional supplementation and selective breeding, all of which act by enhancing the immune response. Currently, control planning is hampered by reliance on the faecal egg count (FEC), which suffers from low accuracy and a nonlinear and indirect relationship with infection intensity and host immune responses. We address this gap by using extensive parasitological, immunological and genetic data on the sheep–Teladorsagia circumcincta interaction to create an immunologically explicit model of infection dynamics in a sheep flock that links host genetic variation with variation in the two key immune responses to predict the observed parasitological measures. Using our model, we show that the immune responses are highly heritable and by comparing selective breeding based on low FECs versus high plasma IgA responses, we show that the immune markers are a much improved measure of host resistance. In summary, we have created a model of host–parasite infections that explicitly captures the development of the adaptive immune response and show that by integrating genetic, immunological and parasitological understanding we can identify new immune-based markers for diagnosis and control

Evaluating the Reliability of FsT-Based Methods Used to Detect the Signature of Selection in Microsatellite Markers Linked to a Selection-Targeted Locus

Random genetic drift affects the distribution of allele frequencies at neutral loci across the genome in a similar way, while selection acts at specific loci and leads to a departure from the expectations of genetic drift at those loci (Cavalli-Sforza 1966). All loci in a genome that do not respond to selection (either directly or through linkage to a selected locus) will have genealogies drawn from the same distribution. In principle it should be possible to identify loci responding to selection (either directly or through linkage) by comparing their level of genetic divergence to that of a neutral model. Lewontin and Krakauer proposed a test for identifying loci subject to selection that worked by estimating the variation in the degree of inbreeding among different loci through the parameter FST (Lewontin and Krakauer 1973). This work examines the effectiveness of a refined version of the method of Lewontin and Krakauer called Fdist (Beaumont and Nichols 1996). Fdist is used to analyse simulated data of microsatellite marker loci linked to a selection-targeted diallelic locus. The evolution of the loci under various symmetrical and asymmetrical island models is investigated by estimations of FsT• Distributions of FST at these target-linked sites· are then compared with observed rates of detection of those loci with Fdist. Results suggest that Fsr-based methods of detecting selection are generally reliable and may be sen,sitive to relatively low selection coefficients provided that population sizes are large and the markers are closely linked to the targets of selection.EThOS - Electronic Theses Online ServiceGBUnited Kingdo