Glucose-6-phosphate dehydrogenase (G6PD) mutations database: Review of the “old” and update of the new mutations

Minucci, Angelo; Moradkhani, Kamran; Hwang, Ming Jing; Zuppi, Cecilia; Giardina, Bruno; Capoluongo, Ettore

doi:10.1016/j.bcmd.2012.01.001

Cited by 257 publications

(267 citation statements)

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“…For example, a number of changes that confer malaria resistance have been observed in the β -globin gene; and the sickle cell allele may plausibly have arisen by up to five independent occurrences of the same base pair mutation at different locations within Africa (Flint et al, 1998; Ralph & Coop, 2010). Another particularly impressive case of convergent evolution is presented by the numerous changes throughout the X-linked G6PD gene, with upward of 50 polymorphic variants (above 1% local frequency) having so far been described that lower the activity of the enzyme (Howes et al, 2013; Minucci et al, 2012). These alleles are now found at a combined frequency of around 8% frequency in malaria endemic areas, rarely exceeding 20% (Howes et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The Role of Standing Variation in Geographic Convergent Adaptation

Ralph

Coop²

2015

The American Naturalist

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The extent to which populations experiencing shared selective pressures adapt through a shared genetic response is relevant to many questions in evolutionary biology. In a number of well studied traits and species, it appears that convergent evolution within species is common. In this paper, we explore how standing, genetic variation contributes to convergent genetic responses in a geographically spread population, extending our previous work on the topic. Geographically limited dispersal slows the spread of each selected allele, hence allowing other alleles – newly arisen mutants or present as standing variation – to spread before any one comes to dominate the population. When such alleles meet, their progress is substantially slowed – if the alleles are selectively equivalent, they mix slowly, dividing the species range into a random tessellation, which can be well understood by analogy to a Poisson process model of crystallization. In this framework, we derive the geographic scale over which a typical allele is expected to dominate, the time it takes the species to adapt as a whole, and the proportion of adaptive alleles that arise from standing variation. Finally, we explore how negative pleiotropic effects of alleles before an environment change can bias the subset of alleles that contribute to the species’ adaptive response. We apply the results to the many geographically localized G6PD deficiency alleles thought to confer resistance to malaria, where the large mutational target size makes it a likely candidate for adaptation from standing variation, despite the selective cost of G6PD deficiency alleles in the absence of malaria. We find the numbers and geographic spread of these alleles matches our predictions reasonably well, consistent with the view that they arose from a combination of standing variation and new mutations since the advent of malaria. Our results suggest that much of adaptation may be geographically local even when selection pressures are homogeneous. Therefore, we argue that caution must be exercised when arguing that strongly geographically restricted alleles are necessarily the outcome of local adaptation. We close by discussing the implications of these results for ideas of species coherence and the nature of divergence between species.

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Section: Introductionmentioning

confidence: 99%

The Role of Standing Variation in Geographic Convergent Adaptation

Ralph

Coop²

2015

The American Naturalist

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“…High frequencies of G6PD-deficient variants have been reported from Africa, Asia, the Mediterranean, and the Middle East [2]. Altogether, 160 mutations, which can result in functional variants presenting with a variety of biochemical and clinical phenotypes, have been described in the G6PD gene [3]. Most G6PD-deficient individuals never experience any signs or symptoms, but some present with episodic hemolytic anemia.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

Tabatabaei

Khorashad

Sakeni

et al. 2015

J Infect Dev Ctries

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Introduction: Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked genetic disorder with a relatively high frequency in malaria-endemic regions. It is an obstacle to malaria elimination, as primaquine administered in the treatment of malaria can cause hemolysis in G6PD-deficient individuals. This study presents information on the prevalence of G6PD deficiency in Sistan and Balouchetsan province, which hosts more than 90% of Plasmodium vivax malaria cases in Iran. This type of information is needed for a successful malaria elimination program. Methodology: A total of 526 students were randomly recruited through schools located in southeast Iran. Information was collected by interviewing the students using a structured questionnaire. Blood samples taken on filter papers were examined for G6PD deficiency using the fluorescent spot test. Results: Overall, 72.8% (383/526) of the subjects showed normal G6PD enzyme function. Mild and severe G6PD deficiency was observed in 14.8% (78) and 12.2% (64) of subjects, respectively. A total 193/261 males (73.9%) and 190/265 (72%) females had normal enzyme activity. Mild G6PD deficiency was observed in 10.8% (28) and 18.9% (50) of male and female subjects, respectively. However, in comparison with females, a greater proportion of males showed severe enzyme deficiency (15.3% versus 9.1%). All these differences were statistically significant (p < 0.006). Conclusions: G6PD deficiency is highly prevalent in southeast Iran. G6PD-deficient individuals are susceptible to potentially severe and lifethreatening hemolytic reactions after primaquine treatment. In order to achieve malaria elimination goals in the province, G6PD testing needs to be made routinely available within the health system.

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“…However, the mechanism of action of methylene blue is dependent on the intracellular capacity for NADP/NADPH recycling, and as the PPP is the only source of NADPH in RBCs, methylene blue treatment to reduce MetHb relies on G6PD enzyme activity. G6PD deficiency is found in around 5% of the world’s population, with more than 180 genetic variants described that confer varying degrees of enzyme deficiency [48,52]. Methylene blue is therefore an unsuitable treatment option for methemoglobinemia in G6PD-deficient individuals, and has been associated with hemolysis likely caused by the exacerbation of oxidative stress in RBCs deficient in the G6PD enzyme.…”

Section: Resultsmentioning

confidence: 99%