Linkage Group Selection – A fast approach to the genetic analysis of malaria parasites

Genetic analysis of malaria parasites has shown that the mechanisms of inheritance in these organisms are classically Mendelian. In other words, alleles of genes at different loci recombine, and alleles at the same gene locus segregate, in the progeny of a genetic cross between two genetically distinct lines of malaria parasite. Importantly, such progeny are haploid in the first filial generation following genetic crossing. Consequently, genetic analysis, including linkage analysis, can be done directly upon the cloned cross progeny. Linkage analysis conducted upon the progeny of genetic crosses between malaria parasites can lead to the location of a single gene controlling a specific phenotype, as has been achieved to identify the gene for chloroquine resistance in Plasmodium falciparum. The work involved, however, is extremely labour intensive. It involves the generation of many hundreds, to a thousand or so, of independent recombinant clones from the cross progeny and the biological characterisation, and genetic typing for hundreds of molecular genetic markers of each such clone. We discuss here a fast-track method for identifying genes controlling specific phenotypes, e.g. drug resistance/sensitivity. It involves the mass screening with quantitative molecular genetic markers of the uncloned progeny of a genetic cross following its growth under a selection pressure representing the phenotype of interest. We have called the method Linkage Group Selection.