Malaria, a contagious disease resulting from Plasmodium parasites, is among the major world-scale health issues. Regardless of the initiatives targeted at discovering an ideal way to manage the disease, the success has been thwarted by the emergence of parasite drug resistance and mosquito resistance to insecticides. This project concentrates on the genetic investigation of resistance to murine malaria induced by the lethal Plasmodium berghei ANKA utilizing a wild-derived-inbred strain (WDIS). The purpose of this dissertation was to exploit the genetic diversity displayed amongst WDIS for identifying loci contributing to resistance/susceptibility to murine malaria..
The project included a genome-wide polymorphism questionnaire using microsatellite markers performed on 10 WDIS. Comparisons of these strains to laboratory inbred strains validated a higher rate of polymorphism among the WDIS. We deduce that these WDIS signify repositories of unique naturally occurring genetic variability that could turn out to be important for the research of complex phenotypes. Following that, we employed the WDIS to find novel phenotypes linked to malaria pathogenesis. While the majority of lab traces were vunerable to experimental cerebral malaria (ECM) after infection with P. berghei ANKA, several WDIS were found to be resistant…
Contents
Introduction
Malaria
An overview of the disease problem Plamodium life cycle
Clinical manifestations
Genetic control of malaria
Genetic analysis of complex traits
Genetic factors influencing malaria infection in human populations
Host genetics in other infectious diseases
Animal models of malaria infection
Genetic analysis of quantitative traits
Genetic linkage analysis of murine malaria
Wild-derived inbred mouse strains
Discussion
General strategy
Genome-wide polymorphism survey in ten wild-derived inbred strains
Phenotype screening of wild-derived inbred strains with P. berghei ANKA
Segregation of malaria phenotypes
Genetic mapping of resistance to cerebral malaria
Genetic mapping of malaria survival
The Berr loci
Berr1
Berr2
Berr3
Berr4
Genetic interaction among the Berr loci
Establishment of Berr congenic strains
Concluding Remarks
Source: Umea University
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