Genetic determinants of selectivity of erythrocyte invasion in the human malaria parasite Plasmodium falciparum

Alghamdi, Sultan Ahmed (2015) Genetic determinants of selectivity of erythrocyte invasion in the human malaria parasite Plasmodium falciparum. PhD thesis, University of Glasgow.

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The aim of this study was to investigate the genetic basis of selectivity in invasion of the red blood cells by the human malaria parasite Plasmodium falciparum. Multiple invasions of a single host red blood cell by more than one merozoite, which can be described or assessed in terms of the selectivity index (SI), has been reported to be related to the severity of malaria disease. In this study, selectivity index, defined as the ratio of the number of multiply-infected red cells observed to that expected from random invasion, as modelled by a Poisson distribution was determined for certain clones of P.falciparum. SI was measured under static and shaking culturing conditions for P. falciparum clones 3D7 and HB3 and 18 progeny clones derived from a genetic cross between these two parasite clones. P. falciparum clone 3D7 was found to have a significantly lower SI than HB3 under both static and shaking culture conditions. There was no relationship between SI and days in continuous culture for clone 3D7 under shaking and static conditions; the phenotype therefore appears to be stable over time. The genetic basis of the difference in selectivity index between P. falciparum clones 3D7 and HB3 was investigated in progeny clones from a cross between these two clones, to ascertain the inheritance pattern of the phenotype. Under static conditions, ten progeny clones had a selectivity index lower than either parent, one progeny clone had higher selectivity index than both parent, and six progeny clones had selectivity index intermediate between the parents . Under shaking conditions, fifteen progeny clones were observed to have a selectivity index lower than either parent. These observations suggest the involvement of more than one parasite gene in selectivity index. A Quantitative Trait Locus (QTL) analysis was performed in order to identify genomic regions influencing SI in the progeny clones. The highest LOD score of 5.06 was obtained for a QTL on chromosome 13 for SI measured in parasites cultured under shaking conditions. This QTL denoted, PF_SI_1, extends for approximately 100kb on chromosome 13 and contains 19 open reading frames. This finding indicates the presence of a gene or genes on chromosome 13 that influence the parasite’s selection of erythrocytes for invasion.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QH Natural history > QH426 Genetics
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Parasitology
Supervisor's Name: Ranford-Cartwright, Dr. Lisa C
Date of Award: 2015
Unique ID: glathesis:2015-6605
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 18 Aug 2015 09:20
Last Modified: 15 Aug 2016 12:30

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