Tight genetic linkage between the kdr insecticide resistance trait and a voltage-sensitive sodium channel gene in the house fly

The kdr insecticide resistance trait in the house fly, Musca domestica, confers resistance to the rapid paralysis (knockdown) and lethal effects of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and pyrethroids. Flies with the kdr trait exhibit reduced neuronal sensitivity to these compounds, which are known to act at voltage-sensitive sodium channels of nerve membranes. To test the hypothesis that a mutation in a voltage-sensitive sodium channel gene confers the kdr phenotype, we have cloned genomic DNA corresponding to a segment of the house fly homologue of the para sodium channel gene of Drosophila melanogaster, identified restriction-site polymorphisms within this segment between the kdr strain 538ge and an inbred insecticide-susceptible lab stain, and developed a sensitive polymerase chain reaction-based diagnostic procedure to determine the sodium channel genotype of individual flies. A genetic linkage analysis performed with these molecular markers shows that the kdr trait is tightly linked (within about 1 map unit) to the voltage-sensitive sodium channel gene segment exhibiting the DNA sequence polymorphism. These findings provide genetic evidence for a mutation at or near a voltage-sensitive sodium channel gene as the basis for kdr resistance.