Exploiting genetic variation to discover genes involved in important disease phenotypes

Elucidating the underlying genetic determinants of disease pathology is still in the early stages for many pathogenic parasites. There have, however, been a number of advances in which natural genetic diversity has been successfully utilized to untangle the often complex interactions between parasite and host. In this chapter we discuss various methods capable of exploiting this natural genetic variation to determine genes involved in phenotypes of interest, using virulence in the pathogenic parasite Trypanosoma brucei as a case study. This species is an ideal system to benefit from such an approach as there are several well-characterized laboratory strains; the parasite undergoes genetic exchange in both the field and the laboratory, and is amenable to efficient reverse genetics and RNAi.