Ovine Disease Resistance: Integrating Comparative and Functional Genomics Approaches in a Genome Information-Poor Species

Abstract

In combination with goats, sheep represent the two most numerous agricultural species for which no cultural or ethical restrictions apply in their use as a source for milk, fibre and red meat. Particularly, in the developing world these species often represent the sole asset base for small-holder livestock farmers. Despite their global significance, genomic tools and approaches in disease resistance have lagged behind the efforts in the economically more influential beef and dairy cattle industries. In particular, infectious diseases have a significant economic impact on livestock production systems worldwide. The most frequently investigated diseases in sheep have focused on the economically important burdens including gastrointestinal nematodes, dermatophilosis, footrot, myiases and fasciolosis. In this study we describe the use of Indonesian Thin Tail sheep (ITT) as a resource which has been shown to have innate and acquired resistance to tropical fasciolosis (Fasciola gigantica). Using the contrast between the resistant ITT and the highly susceptible Merino in a combined functional and comparative genomics approach, we have identified putative QTL (quantitative trait loci) for an extensive panel of parasite and immune response phenotypes and putative resistance pathways and effector molecules. On refinement of candidate gene analyses and effector mechanisms we propose to map these in the economically important target species, namely cattle and buffalo. In addition we exploit the relative susceptibility of ITT sheep to temperate fasciolosis (Fasciola hepatica) to contrast parasite–host interactions and identify parasite immune evasion strategies to boost the discovery of new vaccine candidates and effector pathways, which may be amenable to exogenous control. The study highlights the power and utility of direct gene discovery in ruminant model systems. To overcome the shortage of genomic tools required for such investigations, we have drawn on the development of integrated comparative maps and alignment H.W. Raadsma Reprogen-Centre for Advanced Technologies in Animal Genetics and Reproduction, Faculty of Veterinary Science, University of Sydney, Camden NSW, Australia J.P. Gustafson et al. (eds.), Genomics of Disease, 89 C © Springer Science+Business Media, LLC, 2008 90 H.W. Raadsma et al. to the genome information–rich species such as human, murine and recently cattle. Similarly the use of bovine transcriptome tools have shown cross utility in sheep. The only species-specific requirement is the development of genome-wide high resolution SNP mapping tools which are now under development.