Comparative genomics and host resistance against infectious diseases

The large size and complexity of the human genome have limited the identifi cation and functional characterization of components of the innate immune s ystem that play a critical role in front-line defense against invading micr oorganisms. However, advances in genome analysis (including the development of comprehensive sets of informative genetic markers, improved physical ma pping methods, and novel techniques for transcript identification) have red uced the obstacles to discovery of novel host resistance genes. Study of th e genomic organization and content of widely divergent vertebrate species h as shown a remarkable degree of evolutionary conservation and enables meani ngful cross-species comparison and analysis of newly discovered genes. Appl ication of comparative genomics to host resistance will rapidly expand our understanding of human immune defense by facilitating the translation of kn owledge acquired through the study of model organisms. We review the ration ale and resources for comparative genomic analysis and describe three examp les of host resistance genes successfully identified by this approach.