Genetic variation in parasitic nematodes and its implications.

An absolute pre-requisite for a genetic response to a selective pressure is genetic variation within the population under selection. Helminth populations are clearly able to respond to selective pressures and must, therefore, be genetically heterogeneous. While not quite tautological, this is at best indirect evidence for the existence of genetic variation but there are few examples of well documented helminth phenotypic variation with a proven genetic basis. Isozyme analysis has provided more direct evidence for variation but attempts to link this variation to responses to selection or to identify the forces maintaining that variation have been largely unsuccessful. Thus there is a clear need for new techniques. The recent application of PCR and direct sequencing technology to the study of helminth genetics has allowed the genotypes of individual worms to be determined and the first direct measurements of allele frequencies to be made in this group of organisms. In addition, the application of genetic and molecular data from Caenorhabditis elegans is a potentially rich source of new markers. These techniques do not require that the genetic basis of the phenotype in question be known since a large number of loci can be examined and selection detected through changes in the frequency of anonymous linked marker loci. Phenotypes with complex genetic bases can, therefore, be analysed. I have applied these techniques to the study of anthelmintic resistance genetics and others have applied them to the genetics of inhibited development in Ostertagia. Other phenotypes that are of great interest are the potential for selection of resistance to vaccination and the use of genetically resistant hosts. The ease with which helminths have countered all classes of anthelminitics and the apparently high levels of polymorphism in helminth populations suggest that immunological control methods may also prove to be vulnerable to the adaptive capabilities of the parasite. Evidence from a mouse-helminth model system has already provided evidence that worms can meet the challenge.