Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.654392
Title: The genetics of drug resistance in malaria parasites
Author: MacLeod, R. A. F.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1978
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Abstract:
A genetic study of resistance to sulphadiazine and pyrimethamine was carried out in the rodent malaria parasite Plasmodium chabaudi. A number of lines resistant to pyrimethamine were obtained by direct exposure to the drug and these appeared to comprise a homogeneous group with an increased growth requirement for PABA. Crosses performed using these lines suggested that resistance had arisen as a result of mutation in the same gene. A number of lines resistant to sulphadiazine were obtained either by direct exposure to the drug or following PABA restriction. (A phenotypically indistinguishable example of this type was also obtained by exposure to pyrimethamine.) Other evidence suggested that at least two types of mutation could produce sulphadiazine resistance. An example of one of these was later shown to segregate in a simple Mendelian fashion. A number of double mutant lines were obtained following the superimposition of sulphadiazine resistance on pyrimethamine resistance or vice versa. One such line was later crossed with a wild line and both types of single gene mutant were detected among the products of the cross. The reverse process was mimicked when two single gene mutants were crossed together. There appeared to be free recombination between the genetic elements conferring resistance to pyrimethamine and sulphadiazine. Estimates of the rates of acquisition are presented for each type of resistance and the extent to which each of these represent true mutation rates is discussed. During the development of a rat adapted line of P. chabaudi (intended for use as an additional selective marker) it was discovered that gametocytogenesis was enhanced in rats and consequently this host was later used as the rodent carrier in crosses prior to cyclical passage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.654392  DOI: Not available
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