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Author: Christian Frech
Publisher:
ISBN:
Category : Comparative genomics
Languages : en
Pages : 0
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Book Description
With over 200 million infections and up to one million deaths every year, malaria remains one of the most devastating infectious diseases affecting humans. Over the last few years, complete genome sequences of both human and non-human malaria parasite species have become available, adding comparative genomics to the toolbox of molecular biologists to study the genetic basis of human virulence. In this thesis, I computationally compared the published genomes of seven malaria parasite species with the aim to gain new insights into genes underlying human virulence. This comparison was performed using two complementary approaches. In the first approach, I used whole-genome synteny analysis to find genes present in human but not non-human malaria parasites. In the second approach, I first clustered virulence-associated genes into gene families and then examined these gene families for species-specific differences. Both comparisons resulted in interesting gene lists. Synteny analysis identified three key enzymes of the thiamine (vitamin B1) biosynthesis pathway to be present in human but not rodent malaria parasites, indicating that these two groups of parasites differ in their ability to synthesize vitamin B1 de novo. My gene family classification exposed within the largest and highly divergent surface antigen gene family pir a group of unusually well conserved orthologs, which should be considered as high-priority targets for experimental characterization and vaccine development. In conclusion, this thesis highlights genes and pathways that are different between human and non-human malaria parasites and therefore could play important roles in human virulence. Experimental studies can now be initiated to confirm virulence-associated functions and to explore their potential value for drug and vaccine development.
Author: Christian Frech
Publisher:
ISBN:
Category : Comparative genomics
Languages : en
Pages : 0
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Book Description
With over 200 million infections and up to one million deaths every year, malaria remains one of the most devastating infectious diseases affecting humans. Over the last few years, complete genome sequences of both human and non-human malaria parasite species have become available, adding comparative genomics to the toolbox of molecular biologists to study the genetic basis of human virulence. In this thesis, I computationally compared the published genomes of seven malaria parasite species with the aim to gain new insights into genes underlying human virulence. This comparison was performed using two complementary approaches. In the first approach, I used whole-genome synteny analysis to find genes present in human but not non-human malaria parasites. In the second approach, I first clustered virulence-associated genes into gene families and then examined these gene families for species-specific differences. Both comparisons resulted in interesting gene lists. Synteny analysis identified three key enzymes of the thiamine (vitamin B1) biosynthesis pathway to be present in human but not rodent malaria parasites, indicating that these two groups of parasites differ in their ability to synthesize vitamin B1 de novo. My gene family classification exposed within the largest and highly divergent surface antigen gene family pir a group of unusually well conserved orthologs, which should be considered as high-priority targets for experimental characterization and vaccine development. In conclusion, this thesis highlights genes and pathways that are different between human and non-human malaria parasites and therefore could play important roles in human virulence. Experimental studies can now be initiated to confirm virulence-associated functions and to explore their potential value for drug and vaccine development.
Author: Jane M. Carlton
Publisher: Caister Academic Press Limited
ISBN: 9781908230072
Category : Medical
Languages : en
Pages : 0
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Book Description
This wealth of genome sequence data has provided researchers with a powerful new tool, comparative genomics, which has revolutionised research in this area.
Author: R. Killick-Kendrick
Publisher: Elsevier
ISBN: 0323150578
Category : Medical
Languages : en
Pages : 435
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Book Description
Rodent Malaria reviews significant findings concerning malaria parasites of rodents, including their taxonomy, zoogeography, and evolution, along with life cycles and morphology; genetics and biochemistry; and concomitant infections. This volume is organized into eight chapters and begins by sketching out the history of the discovery of rodent as well as aspects of parasitology, immunology, and chemotherapy. These concepts are investigated two decades following Ignace Vincke's major discovery and Meir Yoeli's successful establishment of the method of cyclical transmission of the parasite. The following chapters focus on the taxonomy and systematics of the subgenus Vinckeia, with reference to the concepts of species and subspecies of animals and the degree to which they apply to malaria parasites, in particular to those of rodents. The discussion then shifts to how the rodent malaria parasites provide a unique insight into the subcellular organization of Plasmodium species, the use of rodent malaria as an experimental model to study immunological responses, and infectious agents that interact with malaria parasites. The book concludes with a chapter on malaria chemotherapy, with emphasis on the value of rodent malaria in antimalarial drug screening and the use of antimalarial drugs as biological probes. This book will be of interest to protozoologists and physicians as well as those from other disciplines including biochemistry, immunology, pharmacology, cell biology, and genetics.
Author: Sesh A. Sundararaman
Publisher:
ISBN:
Category :
Languages : en
Pages : 292
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Book Description
African great apes are infected with at least six species of P. falciparum-like parasites, including the ancestor of P. falciparum. Comparative studies of these parasites and P. falciparum (collectively termed the Laverania subgenus) will provide insight into the evolutionary origins of P. falciparum and identify genetic features that influence host tropism. Here we show that ape Laverania parasites do not serve as a recurrent source of human malaria and use novel enrichment techniques to derive near full-length genomes of close and distant relatives of P. falciparum. Using a combination of single template amplification and deep sequencing, we observe no evidence of ape Laverania infections in forest dwelling humans in Cameroon. This result supports previous findings that ape Laverania parasites are host specific and have successfully colonized humans only once. To understand the determinants of host specificity and identify genetic characteristics unique to P. falciparum, we develop a novel method for selective enrichment of Plasmodium DNA from sub-microscopically infected whole blood samples. We use this technique to enrich for Laverania genomic DNA from chimpanzee blood samples and assemble near full length genomes for both close (P. reichenowi) and distant (P. gaboni) relatives of P. falciparum. Comparative analyses of these genomes to P. falciparum identify features that are conserved across the Laverania subgenus, including the expansion of the FIKK kinases and the presence of var-like multigene families in all Laverania species. Our analyses also identify genetic features that are unique to P. falciparum, such as a very low within-species diversity and a complex evolutionary history of the essential invasion genes RH5 and CyRPA. This dissertation lays the groundwork for future comparative analyses of the Laverania subgenus including population genomic analyses of ape parasites and comparisons of P. falciparum to its ancestor, P. praefalciparum.
Author: Manoj Kumar Yadav
Publisher:
ISBN: 9783659683626
Category :
Languages : en
Pages : 144
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Book Description
Malaria is a threat to mankind and responsible for millions of cases of morbidity and mortality worldwide. Plasmodium parasite is responsible for causing disease. This work investigates and reveals the hidden information inside the parasite genomes using comparative genome analysis and codon usage bias study. The possibility of using variable surface proteins as a common drug target has been checked in both the human infecting Plasmodium species and it was found that variable surface proteins cannot be used as a common drug target due to existence of sequential and structural differences at both the genome and proteome level. Metabolic network information is also utilized in this piece of work for identifying new drug targets. Further in silico approaches viz. molecular modeling, structure-based 3D pharmacophore model generation, virtual screening and docking etc. were also utilized to find the drug prototypes.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 9780309045278
Category : Medical
Languages : en
Pages : 312
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Book Description
Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Author: Andrew P. Waters
Publisher: Caister Academic Press Limited
ISBN:
Category : Medical
Languages : en
Pages : 578
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Book Description
The completion of the Plasmodium falciparum genome sequence in late 2002 heralded a new era in malaria research. The search began in earnest for new drugs and vaccines to combat malaria, a disease which afflicts up to 500 million people worldwide and is responsible for the deaths of more than one million people each year. The new genomic data is aiding a greater understanding of the living parasite and its interaction with the insect vector and human host. In this book internationally renowned experts provide up-to-date reviews of the most important aspects of post-genomic malaria research. Topics covered include: the P. falciparum genome and model parasites, bioinformatics and genome databases, microsatellite analysis, analysis of chromosome structure, cell cycle to RNA polymerase I and II mediated gene expression, role of the nuclear genome, the parasite surface and cell biology, and much more. The book is essential to all researchers working in this highly topical field and is recommended reading for scientists in other areas of biology and medicine.
Author: Andrew Taylor Bright
Publisher:
ISBN: 9781303461682
Category :
Languages : en
Pages : 291
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Book Description
Plasmodium vivax causes 25-40% of malaria cases worldwide, yet research on this human malaria parasite has been neglected. Nevertheless, the recent publication of the P. vivax reference genome now allows genomics and systems biology approaches to be applied to this pathogen. We show here that whole genome analysis of the parasite can be achieved directly from ex vivo-isolated parasites, without the need for in vitro propagation. Additionally, we show that in-solution hybridization capture can be used to extract P. vivax DNA from human contaminating DNA in the laboratory without the need for on-site leukocyte filtration. Utilizing a whole genome capture method, we were able to enrich P. vivax DNA from bulk genomic DNA from less than 0.5% to a median of 55% (range 20%-80%). This level of enrichment allows for efficient analysis of the samples by whole genome sequencing and does not introduce any gross biases into the data. These techniques were subsequently used to investigate the dormant hepatic stages, known as hypnozoites, in P. vivax. This unique parasite stage is an important reservoir of infection and a critical barrier to malaria eradication. At present there are no biomarkers to identify this tissue stage and estimates of the prevalence of infections due to hypnozoites are confounded by the inability to distinguish between new and relapsing infection. Here we performed whole genome sequencing of consecutive P. vivax relapse infections using material from a patient who experienced three episodes of P. vivax malaria over 33 months in a non-endemic country. Based on patient medical history and analysis of single nucleotide variants (SNV), it was determined that two of the infections were caused by reactivation of single hypnozoites. We observe that the three recurring infections were caused by meiotic siblings. This indicates that a single sexual cross in the mosquito is capable of creating multiple distinct parasite populations, thus definitively demonstrating that the result of parasite sexual replication and meiosis in the mosquito, the oocyst, is comprised of parasites descended from a single tetrad.
Author: Percy Cyril Claude Garnham
Publisher:
ISBN:
Category : Apicomplexa
Languages : en
Pages : 1234
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Book Description
Author: Jeffrey R. Johnson
Publisher:
ISBN:
Category : Plasmodium falciparum
Languages : en
Pages : 336
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Book Description
Abundant genome sequence data for several species of Plasmodium has pushed malaria research into its own post-genomics era. The first genome sequence of a Plasmodium parasite was published in 2002 for the most deadly human species of the malaria-causing agent, Plasmodium falciparum , illustrating for the first time the extent to which Plasmodium differs from other organisms. Containing an A/T base-pair composition of over 80%, with A/T content in non-coding regions elevated to over 95%, and over 60% of annotated genes lacking significant sequence similarity to those from other organisms, the majority of the Plasmodium genome remains a mystery. Large-scale efforts to measure gene and protein expression amongst the many stages of the parasite's complex life cycle have generated prolific amounts of data that are generally analyzed separately. This thesis represents an effort to analyze large-scale data sets derived from different platforms, and for different species, through bioinformatics integration and interpretation. First, by comparing gene and protein expression data collected across both asexual and sexual stages of Plasmodium development, post-transcriptional regulatory controls were discovered for families of genes sharing similar function. Second, through integrating data from proteome analyses of three Plasmodium species acquired at various stages across the parasite life cycle, a profile of conserved protein expression was built across the Plasmodium genus. From this analysis it was found that the distribution of membrane proteins appeared to be associated with conserved proteins exhibiting discordant expression among the species analyzed, suggesting that species differences have arisen not only from diversity generated by species-specific genes, but also by the discordant expression of conserved genes. Finally, new methods for comparative proteomic analysis are presented, which use annotated libraries of tandem mass spectra and hierarchical clustering to identify representative spectra prior to spectrum identification.
