The effect of selection for nematode resistance on mhc class II diversity

All vertebrates have an immune system that protects them from infectious organisms. A key component of the immune response is the major histocompatibility complex (MHC). This complex contains two sets of highly variable genes that code for class I and class II proteins. These proteins activate the immune system to respond to invading parasites. Each individual has a distinct set of MHC proteins that allow recognition of a specific set of parasite molecules. The major disease faced by sheep is infection by roundworms. There is substantial genetic variation among sheep in resistance to roundworms. Farmers have started to identify and breed from sheep with enhanced resistance to roundworms. Sheep with a particular combination of class II MHC genes are more resistant to roundworms. These class II MHC genes may also play a role in fighing other diseases and most scientists agree that populations that maintain a diverse array of class II genes are more resistant to most infectious and parasitic diseases. The goal of this project is to determine whether selective breeding for resistance to nematodes will cause a noticeable loss of mhc diversity. We will do this by estimating the size of the effect that each class II gene has on nematode resistance then using mathematical models of the selection process to estimate the influence of selection on mhc diversity. The outcome of this research will improve our ability to breed roundworm-resistant sheep without adverse effects on susceptibility to other diseases.

All grazing sheep are exposed to nematodes. Even moderate infection reduces growth, decreases carcass quality and compromises animal health and welfare. Lambs vary in susceptibility to nematode infection and this operates largely through genetic variation in immune responsiveness. IgA and IgE antibodies regulate nematode growth and survival. Class II genes in the major histocompatibility complex influence antibody specificity and variation among class II genes has been repeatedly linked to and associated with resistance to nematode infection. Most immunologists believe that populations with high levels of diversity at mhc class II loci are healthier and better able to resist disease. This project aims to identify the influence of selection for nematode resistance on mhc diversity. We propose to use direct sequencing to characterise mhc diversity in a population of sheep that has been characterised for nematode resistance. Statistical modelling will then be used to estimate the effect of each allele at each locus on faecal egg counts. Mathematical modelling will examine the effects of selecting sheep for reduced faecal egg count on mhc class II diversity. The outcome of this research will improve our ability to breed roundworm-resistant sheep without adverse effects on susceptibility to other diseases.