Genetic analysis of murine malaria

Malaria, a contagious disease brought on by Plasmodium parasites, is probably the major world-scale health issues. Inspite of the efforts targeted at finding an ideal way to manage the illness, the success has been thwarted via the emergence of parasite drug resistance and mosquito potential to deal with insecticides. This thesis concentrates on the genetic analysis of ability to resist murine malaria induced by way of the lethal Plasmodium berghei ANKA utilizing a wild-derived-inbred strain (WDIS). The purpose of this thesis was to exploit the genetic diversity represented among WDIS for identifying loci adding to resistance/susceptibility to murine malaria.The task included a genome-wide polymorphism survey using microsatellite markers performed on 10 WDIS. Comparisons of those strains to laboratory inbred strains confirmed better pay of polymorphism among the list of WDIS. We conclude that these particular WDIS represent databases of unique naturally sourced genetic variability that will show to be invaluable for that study of complex phenotypes. Next, we used the WDIS to look for novel phenotypes linked to malaria pathogenesis. Whereas most laboratory strains were vulnerable to experimental cerebral malaria (ECM) after infection with P. berghei ANKA, several WDIS were found being resistant…

Contents: Genetic analysis of murine malaria

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
Acknowledgements
References
Papers I-IV