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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomerase, a specialized cellular reverse transcriptase, compensates for chromosome shortening during the proliferation of most eucaryotic cells and contributes to cellular immortalization. The mechanism used by the single-celled protozoan malaria parasite Plasmodium falciparum to complete the replication of its linear chromosomes is currently unknown. In this study, telomerase activity has for the first time been identified in cell extracts of P. falciparum. The de novo synthesis of highly variable telomere repeats to the 3' end of DNA oligonucleotide primers by plasmodial telomerase is demonstrated. Permutated telomeric DNA primers are extended by the addition of the next correct base. In addition to elongating preexisting telomere sequences, P. falciparum telomerase can also add telomere repeats onto nontelomeric 3' ends. The sequence GGGTT was the predominant initial DNA sequence added to the nontelomeric 3' ends in vitro. Poly(C) at the 3' end of the oligonucleotide significantly alters the precision of the new telomerase added repeats. The efficiency of nontelomeric primer elongation was dependent on the presence of a G-rich cassette upstream of the 3' terminus. Oligonucleotide primers based on natural P. falciparum chromosome breakpoints are efficiently used as telomerase substrates. These results imply that P. falciparum telomerase contributes to chromosome maintenance and to de novo telomere formation on broken chromosomes. Reverse transcriptase inhibitors such as dideoxy GTP efficiently inhibit P. falciparum telomerase activity in vitro. These data point to malaria telomerase as a new target for the development of drugs that could induce parasite cell senescence.
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PMID:Plasmodium falciparum telomerase: de novo telomere addition to telomeric and nontelomeric sequences and role in chromosome healing. 944 88

We investigated the variability of pericentromeric chromatin of chromosome 2 in ovarian nurse cells (trophocytes) in two laboratory lines of malaria mosquito Anopheles atroparvus V. Tiel and in their hybrids. One line had been raised by means of sib inbreeding, the other kept at constantly high population density. The inbreeding was shown to result in an increased percentage of chromosomes bearing an achromatinic zone in the centromeric region, which resulted in chromosome breakage. Toxicological tests demonstrated an increase in the sensitivity of the progeny of females with abnormal morphotypes of chromosome 2 to the entomopathogenic bacterium Bacillus thuringiensis israelensis. The appearance of the achromatinic zone is attributed to local chromatin underreplication accompanying chromosome polytenization. Possible reasons for this phenomenon and its implication for adaptation are discussed.
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PMID:[Variability of pericentromeric chromatin in chromosome 2 of ovarian nurse cells during inbreeding in Anopheles atroparvus V.Tiel]. 974 41

Tyrosine kinase sequences were identified and characterized in Anopheles gambiae, the major vector of malaria in subsaharan Africa. One of these sequences has the characteristics expected for a homologue of the Drosophila sevenless gene, which is necessary for R7 photoreceptor cell fate determination in the developing compound eye. The putative Anopheles sevenless gene homologue is located in a telomeric region of the X chromosome and is expressed in the head of late larval and pupal stage mosquitoes. Identification of the Anopheles homologue of the sevenless gene is a first step towards the development of a dominant phenotypic marker that could be used for detecting transformed Anopheles mosquitoes in a wide variety of genetic backgrounds and, as such, could be used in the development of transgenic mosquitoes for the control of parasite transmission. Preliminary evidence for sevenless sequences were also found in DNA from blackfly, Mediterranean fruit fly and the honeybee.
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PMID:Identification and characterization of a putative sevenless homologue in the malaria vector Anopheles gambiae. 1038 Jan 11

We describe a transfection system that induces terminal deletions at specific chromosome ends in malaria parasites using a linear construct containing telomeric repeats at one end and plasmodial sequences able to drive homologous recombination at the other. A site-specific deletion was generated at one extremity of chromosome 5 of Plasmodium berghei, which was stably maintained in the parasite population selected after transfection. The telomeric repeat array introduced with the construct reached the average length observed in natural telomeres of Plasmodium, indicating that in vivo telomere addition occurred at the newly formed extremity. The expression of a mutant dhfr/ts gene conferring pyrimethamine resistance, used as a selectable marker, was not affected by the proximity to the telomeric sequences, either in the presence or absence of drug pressure. In addition, no transcriptional silencing was observed on insertion of the mutant dhfr/ts gene either in subtelomeric or internal positions that are transcriptionally silent in blood-stage parasites. This suggests that the activity of its promoter is not affected by the chromatin organization of the chromosomal context.
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PMID:Targeted terminal deletions as a tool for functional genomics studies in Plasmodium. 1098 59

In the protozoan malaria parasite, Plasmodium falciparum, the telomere-associated sequences (TASs) of the 14 linear chromosomes display a similar higher order organization and form clusters of four to seven telomeres localized at the nuclear periphery. Experimental evidence has shown that the physical tethering of chromosome ends enhances the ectopic recombination between gene families involved in antigenic variation and parasite sequestration. Using FISH analysis, we observed that chromosome ends lacking the subtelomeric region are usually delocalized from telomere clusters, but still remain at the nuclear periphery. This indicates that subtelomeric DNA is necessary for cluster formation but is not essential for peripheral positioning. Intriguingly, these truncated chromosomes have unusually long telomeric tracts (up to three times longer than average length), showing that TASs play a role in telomere length regulation. On these chromosomes, the newly formed telomere frequently extends from truncated genes leading, in some cases, to the transcription of telomeric DNA. The implications of both subtelomeric gene expression and nuclear architecture in the virulence of this serious human pathogen are discussed.
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PMID:A central role for Plasmodium falciparum subtelomeric regions in spatial positioning and telomere length regulation. 1184 28

The disease outcome in malaria caused by the protozoan parasite Plasmodium is influenced by host genetic factors. To identify host genes conferring resistance to infection with the malaria parasite, we undertook chromosomal mapping using a whole-genome scanning approach in cross-bred mice. NC/Jic mice all died with high parasitemia within 8 days of infection with 1 x 10(5) parasitized erythrocytes. In contrast, 129/SvJ mice all completely excluded malaria parasites from the circulation and remained alive 21 days after infection. We performed linkage analysis in backcross [(NC/Jic x 129/SvJ)xNC/Jic] mice. The Pymr ( Plasmodium yoelii malaria resistance) locus was mapped to the telomeric portion of mouse Chromosome (Chr) 9. This locus controls host survival and parasitemia after infection. The Char1 locus ( P. chabaudi resistance locus 1), controlling host survival and peak parasitemia in P. chabaudi infection, was previously mapped to the same region. This host resistance locus mapping to Chr 9 may represent a ubiquitous locus controlling susceptibility to rodent malaria. Elucidation of the function of this gene will provide valuable insights into the mechanism of host defense against malaria parasite infection.
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PMID:Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice. 1186 5

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.
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PMID:Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. 1236 62

The merozoite surface protein-1 (MSP-1) of the malaria parasite Plasmodium falciparum is a major blood-stage antigen containing highly polymorphic tripeptide repeats in the domain known as block 2 and several non-repetitive domains that are essentially dimorphic. We have analyzed sequence variation in block 2 repeats and in non-repetitive block 17, as well as other polymorphisms within the MSP-1 gene, in clinical isolates of P. falciparum. Repeat haplotypes were defined as unique combinations of repeat motifs within block 2, whereas block 17 haplotypes were defined as unique combinations of single nucleotide replacements in this domain. A new block 17 haplotype, E-TNG-L, was found in one isolate from Vietnam. MSP-1 alleles, defined as unique combinations of haplotypes in blocks 2 and 17 and other polymorphisms within the molecule, were characterized in 60 isolates from hypoendemic Brazil and 37 isolates from mesoendemic Vietnam. Extensive diversity has been created in block 2 and elsewhere in the molecule, while maintaining significant linkage disequilibrium between polymorphisms across the non-telomeric MSP-1 locus separated by a map distance of more than 4 kb, suggesting that low meiotic recombination rates occur in both parasite populations. These results indicate a role for non-homologous recombination, such as strand-slippage mispairing during mitosis and gene conversion, in creating variation in a malarial antigen under strong diversifying selection.
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PMID:Sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-1 (MSP-1) of Plasmodium falciparum. 1256 16

Relapse variants in chronic Plasmodium falciparum infections are antigenically distinct from the parental parasites. The variable antigen PfEMP1 expressed at the surface of the infected erythrocyte (IE) is encoded by the var gene family with approximately 60 copies per haploid genome. Placental isolates commonly express DBLgamma containing subtypes of var genes with homology to either 3D7var5.2 (var(COMMON)) or FCR3var(CSA). Here we report that var(COMMON) related genes are constitutively transcribed in approximately 60% of malaria infected children in Gabon. var(COMMON) is conserved in field isolates over at least 2.1kb. In 3D7 parasites var(COMMON) is present on chromosome 5 (var5.2) and constitutively transcribed in the opposite direction to most other var genes. It lacks a regulatory intron, an acidic terminal segment and ends in telomeric repeat sequences. var(COMMON) encodes a large, hypothetical PfEMP1 of a structure similar to previous placenta-binding PfEMP1s but it is not present at the IE-surface. IE of a 3D7 clone (3D7S8) transcribe var(COMMON) but express a PfEMP1 distinct from var(COMMON) at the surface and adhere to placental tissues through var(COMMON) independent novel mechanisms. Our report suggests that expression of var(COMMON) type genes is not restricted to placental malaria.
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PMID:The 3D7var5.2 (var COMMON) type var gene family is commonly expressed in non-placental Plasmodium falciparum malaria. 1267 27

Microsatellite markers derived from simple sequence repeats have been useful in studying a number of human pathogens, including the human malaria parasite Plasmodium falciparum. Genetic markers for P. vivax would likewise help elucidate the genetics and population characteristics of this other important human malaria parasite. We have identified a locus in a P. vivax telomeric clone that contains simple sequence repeats. Primers were designed to amplify this region using a two-step semi-nested polymerase chain reaction protocol. The primers did not amplify template obtained from non-infected individuals, nor DNA from primates infected with the other human malaria parasites (P. ovale, P. malariae, or P. falciparum). The marker was polymorphic in P. vivax-infected field isolates obtained from Papua New Guinea, Indonesia and Guyana. This microsatellite marker may be useful in genetic and epidemiologic studies of P. vivax malaria.
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PMID:Identification of a polymorphic Plasmodium vivax microsatellite marker. 1464 Apr 96


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