Filarial and malarial parasites are responsible for the most devastating vector-borne infections of humans with over 420 million people affected worldwide and with over 2 million people killed annually. Our long-term objective is to elucidate the molecular basis for vector competence in the transmission of parasitic diseases and to control vector-borne parasitic disease cycles in nature. The advent and development of molecular markers for mosquitoes has allowed the identification of discrete genome regions carrying genes determining the susceptibility of the yellow fever mosquito, Aedes aegypti, to several parasites including the filarial parasite responsible for zoonotic filariasis, dog heartworm, Dirofilaria immitis, the human lymphatic filaroid parasite, Brugia malayi, and the avian malaria parasite, plasmodium gallinaceum. It is our hypothesis that the genes determining vector competence for parasite transmission can be identified and isolated using a combination of fluorescence in situ hybridization (FISH)-based physical mapping and genetic linkage mapping techniques. What we intend to do is to characterize the genome regions by map-base positional cloning strategies using FISH as a primary physical mapping tool and to identify the gene(s) responsible through transcriptional and functional characterization. Since we have identified the QTL regions and have begun contig construction across these regions, here we present details in our research design describing how we will accomplish the map-based positional cloning of genes responsible for Brugia malayi parasite vector competence in Aedes aegypit.
Aim 1 describes how we will construct contigs across the QTL regions.
Aim 2 outlines our strategies for the isolation of transcribed sequences within the regions.
Aim 3 describes our plan for correlating specific mutations with phenotype. The use of multiple strategies ensure a high likelihood of success in identifying the gene(s) for the trait from at least one major region. If the biochemical pathways associated with genes that influence vector susceptibility to parasites can be defined, new chemical control and intervention strategies may be developed and incorporated into current and existing control strategies.
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