Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.642596
Title: The genetics of chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi
Author: Carlton, Jane M.-R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Abstract:
The aim of this work has been to use linkage analysis to determine the chromosomal location of genes involved in chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi. The P. chabaudi genome was found to contain 14 chromosomes. A genetic map of each chromosome was made using DNA markers. Most of the markers were known genes from other species of Plasmodium. Other markers were developed by the RAPD-PCR (random amplified polymorphic DNA-polymerase chain reaction) technique, the first time this method has been developed for use with Plasmodium parasites. In total, more than 100 markers were mapped to individual P. chabaudi chromosomes. Two important markers were cloned from P. chabaudi DNA using PCR. (i) the P. chabaudi homologue (pcmdr1) of the multiple drug resistance gene of P.falciparum (pfmdr 1); this has been implicated in the mechanism of chloroquine-resistance in P. falciparum. (ii) a possible homologue of the P. falciparum marker pS590.7, which has been claimed to be linked to a chloroquine-resistance locus in P. falciparum. 13 genetically distinct clones from the cross were phenotyped for their susceptibility to chloroquine. 8 were found to be resistant and 5 sensitive. These clones were analysed for their inheritance of 46 polymorphic markers. This revealed that neither pcmdr 1 nor the putative ps590.7 homologue were linked to chloroquine resistance in this cross. 12 of the 13 progeny showed linkage disequilibrium with a locus on chromosome 11. Statistical analysis showed the linkage to be significant, with a probability of 0.05>P>0.03. The work submitted here represents the first in-depth genetic analysis of a P. chabaudi cross and identifies a locus which may be involved in the genetic mechanism of chloroquine resistance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.642596  DOI: Not available
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