Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. It has been reported from India more than 30 years ago and the prevalence varies from 0-27% in different caste, ethnic and linguistic groups. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic non-spherocytic hemolytic anemia. Individuals with G6PD deficiency have a selective advantage against falciparum malaria. Thirteen biochemically characterized variants have been reported from India. At the molecular level, G6PD Mediterranean is the most common deficient variant in the caste groups whereas, G6PD Orissa is more prevalent among the tribal of India. The third common variant seen in India is G6PD Kerala-Kalyan.
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PMID:Glucose-6-phosphate dehydrogenase deficiency in India. 1522 63

Emerging species within the primary malaria vector Anopheles gambiae show different ecological preferences and significant prezygotic reproductive isolation. They are defined by fixed sequence differences in X-linked rDNA, but most previous studies have failed to detect large and significant differentiation between these taxa elsewhere in the genome, except at two other loci on the X chromosome near the rDNA locus. Hypothesizing that this pericentromeric region of the X chromosome may be accumulating differences faster than other regions of the genome, we explored the pattern and extent of differentiation between A. gambiae incipient species and a sibling species, A. arabiensis, from Burkina Faso, West Africa, at 17 microsatellite loci spanning the X chromosome. Interspecific differentiation was large and significant across the entire X chromosome. Among A. gambiae incipient species, we found some of the highest levels of differentiation recorded in a large region including eight independent loci near the centromere of the X chromosome. Outside of this region, no significant differentiation was detected. This pattern suggests that selection is playing a role in the emergence of A. gambiae incipient species. This process, associated with efficient exploitation of anthropogenic modifications to the environment, has public health implications as it fosters the spread of malaria transmission both spatially and temporally.
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PMID:Sex-linked differentiation between incipient species of Anopheles gambiae. 1565 9

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked red blood cell enzymopathy common in malaria endemic areas. Individuals affected by this disease show a wide variety of clinical signs of acute hemolytic anemia. Mutations of the G6PD gene in the Malay population with G6PD deficiency in Kelantan, a state in North East Malaysia were studied. Ninety-three individuals with G6PD deficiency were subjected to mutation analysis of the G6PD gene using polymerase chain reaction based techniques of multiplex PCR. Of the ninety-three DNA samples studied, molecular defects were identified in 80 cases (86%). Variants were heterogeneous - 28.7% were found to have a G to A nucleotide change at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan. The other major mutations were G6PD Mediterranean, G6PD Vanua Lava, G6PD Coimbra, G6PD Kaiping, G6PD Orissa, G6PD Mahidol, G6PD Canton and G6PD Chatham. These results showed that there are heterogeneous mutations of the G6PD gene associated with G6PD deficiency and that G6PD Viangchan and G6PD Mediterranean account for the main variants in G6PD deficiency among the Malay population in Malaysia.
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PMID:G6PD Viangchan and G6PD Mediterranean are the main variants in G6PD deficiency in the Malay population of Malaysia. 1590 17

The malaria mosquito Anopheles gambiae s.s. is rapidly becoming a model for studies on the evolution of reproductive isolation. Debate has centered on the taxonomic status of two forms (denoted M and S) within the nominal taxon identified by point mutations in the X-linked rDNA region. Evidence is accumulating that there are significant barriers to gene flow between these forms, but that the barriers are not complete throughout the entire range of their distribution. We sampled populations from across Ghana and southern Burkina Faso, West Africa, from areas where the molecular forms occurred in both sympatry and allopatry. Neither Bayesian clustering methods nor F(ST)-based analysis of microsatellite data found differentiation between the M and S molecular forms, but revealed strong differentiation among different ecological zones, irrespective of M/S status and with no detectable effect of geographical distance. Although no M/S hybrids were found in the samples, admixture analysis detected evidence of contemporary interform gene flow, arguably most pronounced in southern Ghana where forms occur sympatrically. Thus, in the sampled area of West Africa, lack of differentiation between M and S forms likely reflects substantial introgression, and ecological barriers appear to be of greater importance in restricting gene flow.
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PMID:Ecological zones rather than molecular forms predict genetic differentiation in the malaria vector Anopheles gambiae s.s. in Ghana. 1711 Apr 81

CD40L is a type II membrane protein comprised of 261 amino acids. CD40L plays a crucial role in the immune system where it is primarily expressed on activated T cells and triggers immunoglobulin class switching. The genetic disease X-linked hypergammaglobulinemia (HIGM1, XHIGM or XHIM) is caused by mutations in the CD40L gene. Individuals with HIGM1 are susceptible to recurrent infections to pathogens and a relationship has been shown to exist with malaria [Sabeti, P., Usen, S., Farhadian, S., Jallow, M., Doherty, T., Newport, M., Pinder, M., Ward, R., Kwiatkowski, D., 2002a. CD40L association with protection from severe malaria. Genes Immun. 3, 286-291]. In this paper, we phylogenetically examine the promoter region of CD40L in primates and other mammals via phylogenetic shadowing. This analysis revealed several regions of the CD40L promoter that were highly constrained and thereby inferred to be functional. These constrained regions confirmed many known regulatory sites. In addition, a novel, highly constrained upstream region was also identified which had an NF-AT recognition motif. These analyses also showed that the different mammal groups do not share an exactly similar set of promoter binding sites and taxon-specific promoters have evolved.
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PMID:Phylogenetic analysis of the promoter region of the CD40L gene in primates and other mammals. 1727 21

The use of genetic drive mechanisms to replace native mosquito genotypes with individuals bearing antipathogen transgenes is a potential strategy for repressing insect transmission of human diseases such as malaria and dengue. Antipathogen transgenes have been developed and tested, but efficient gene drive mechanisms are lacking. Here we theoretically assess the feasibility of introducing antipathogen genes into wild Aedes aegypti populations by using a naturally occurring meiotic drive system. We consider the release of males having both a Y-linked meiotic drive gene and an X-linked drive-insensitive response allele to which an antipathogen gene is linked. We use mathematical models and computer simulations to determine how the post-introduction dynamics of the antipathogen gene are affected by specific genetic characteristics of the system. The results show that when the natural population is uniformly sensitive to the meiotic drive gene, the antipathogen gene may be driven close to fixation if the fitness costs of the drive gene, the insensitive response allele, and the antipathogen gene are low. However, when the natural population has a small proportion of an X-linked insensitive response allele or an autosomal gene that strongly reduces the effect of the drive gene, the antipathogen gene does not spread if it has an associated fitness cost. Our modeling results provide a theoretical foundation for further experimental tests.
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PMID:Introducing desirable transgenes into insect populations using Y-linked meiotic drive - a theoretical assessment. 1743 7

Deficiency of glucose-6-phosphate dehydrogenase is a very common X-linked genetic disorder though most deficient people are asymptomatic. A number of different G6PD variants have reached polymorphic frequencies in different parts of the world due to the relative protection they confer against malaria infection. People, usually males, with deficient alleles are susceptible to neonatal jaundice, and acute hemolytic anemia, usually during infection, after treatment with certain drugs or after eating fava beans. Very rarely de novo mutations can arise causing the more severe condition of chronic nonspherocytic hemolytic anemia. Altogether 160 different mutations have been described. The majority of mutations cause red cell enzyme deficiency by decreasing enzyme stability. The polymorphic mutations affect amino acid residues throughout the enzyme and decrease the stability of the enzyme in the red cell, possibly by disturbing protein folding. The severe mutations mostly affect residues at the dimer interface or those that interact with a structural NADP molecule that stabilizes the enzyme.
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PMID:G6PD deficiency: the genotype-phenotype association. 1761 Oct 6

Transposable elements represent important tools to perform functional studies in insects. In Drosophila melanogaster, the remobilization properties of transposable elements have been utilized for enhancer-trapping and insertional mutagenesis experiments, which have considerably helped in the functional characterization of the fruitfly genome. In Anopheles mosquitoes, the sole vectors of human malaria, as well as in other mosquito vectors of disease, the use of transposons has also been advocated to achieve the spread of anti-parasitic genes throughout field populations. Here we report on the post-integration behavior of the Minos transposon in both the germ-line and somatic tissues of Anopheles mosquitoes. Transgenic An. stephensi lines developed using the piggyBac transposon and expressing the Minos transposase were tested for their ability to remobilize an X-linked Minos element. Germ-line remobilization events were not detected, while somatic excisions and transpositions were consistently recovered. The analysis of these events showed that Minos activity in Anopheles cells is characterized by unconventional functionality of the transposon. In the two cases analyzed, re-integration of the transposon occurred onto the same X chromosome, suggesting a tendency for local hopping of Minos in the mosquito genome. This is the first report of the post-integration behavior of a transposable element in a human malaria vector.
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PMID:Post-integration behavior of a Minos transposon in the malaria mosquito Anopheles stephensi. 1763 17

G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.
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PMID:Present status of understanding on the G6PD deficiency and natural selection. 1769 98

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, being present in more than 400 million people worldwide. The global distribution of this disorder is remarkably similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. About 140 mutations have been described: most are single base changes, leading to aminoacid substitutions. The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice, and acute haemolytic anaemia, which is usually triggered by an exogenous agent. Some G6PD variants cause chronic haemolysis, leading to congenital non-spherocytic haemolytic anaemia. The most effective management of G6PD deficiency is to prevent haemolysis by avoiding oxidative stress. Screening programmes for the disorder are undertaken, depending on the prevalence of G6PD deficiency in a particular community.
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PMID:Glucose-6-phosphate dehydrogenase deficiency. 1875 69


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