A global network for investigating the genomic epidemiology of malaria The Malaria Genomic Epidemiology Network Nature 2008 456 7223 732 737 10.1038/nature07632

Nature 12/2008; 19079050(456):732-737. DOI: 10.1038/nature07632


Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.

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Available from: Mahamadou Diakite,
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    • "Malaria affects about one quarter of a billion people annually, with up to two-thirds of a million deaths still occurring per year, particularly in sub-Saharan African children below five years of age [1]. Why only a small proportion (1–3%) of Plasmodium falciparum infections progress to severe or fatal episodes [2] while others remain asymptomatic or develop an uncomplicated illness is not yet fully understood. Epidemiological data indicate that about 25% of the risk to Plasmodium infection in Africa is determined by human genetic factors [3]. "
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    ABSTRACT: Background Plasmodium falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical host genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity and improve vaccine development initiatives. Methods The effect of single nucleotide polymorphisms (SNPs) and plasma transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) levels on malaria pathology was investigated in a case–control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Thirty-four malaria candidate polymorphisms, including the sickle cell trait (HbS), were assayed on the Sequenom iPLEX platform while plasma TGF-β and IL-10 levels were measured by sandwich ELISA. Results The study confirms the known protective effect of HbS against severe malaria and also reveals a protective effect of SNPs in the nitrogen oxide synthase 2 (NOS2) gene against malaria infection, anaemia and uncomplicated malaria. Furthermore, ADCY9 rs10775349 (additive G) and ABO rs8176746 AC individuals were associated with protection from hyperpyrexia and hyperparasitaemia, respectively. Meanwhile, individuals with the EMR1 rs373533 GT, EMR1 rs461645 CT and RTN3 rs542998 (additive C) genotypes were more susceptible to hyperpyrexia while both females and males with the rs1050828 and rs1050829 SNPs of G6PD, respectively, were more vulnerable to anaemia. Plasma TGF-β levels were strongly correlated with heterozygosity for the ADCY9 rs2230739 and HBB rs334 SNPs while individuals with the ABO rs8176746 AC genotype had lower IL-10 levels. Conclusion Taken together, this study suggests that some rare polymorphisms in candidate genes may have important implications for the susceptibility of Cameroonians to severe malaria. Moreover using the uncomplicated malaria phenotype may permit the identification of novel pathways in the early development of the disease.
    Malaria Journal 06/2014; 13(1):236. DOI:10.1186/1475-2875-13-236 · 3.11 Impact Factor
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    • "Investigators from multiple disciplines have increased their efforts to use genomic tools to shed light on the complex interplay between genetic and non-genetic factors in disease etiology [1]. The systematic growth of genetic and genomic research initiatives highlights the need to understand and address informed consent practices for genetic studies with diverse populations [2]. "
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    ABSTRACT: Background Studies on informed consent to medical research conducted in low or middle-income settings have increased, including empirical investigations of consent to genetic research. We investigated voluntary participation and comprehension of informed consent among women involved in a genetic epidemiological study on breast cancer in an urban setting of Nigeria comparing women in the case and control groups. Methods Surveys were administered in face-to-face interviews with 215 participants following their enrollment in the genetic study (106 patients, 109 controls). Audio-taped in-depth interviews were conducted with a sub-sample of 17 (8%) women who completed the survey. Results The majority of all participants reported being told that participation in the genetic study was voluntary (97%), that they did not feel pressured to participate in the study (99%), and that they could withdraw from the study (81%). The majority of the breast cancer patients (83%) compared to 58% of women in the control group reported that the study purpose was to learn about the genetic inheritance of breast cancer (OR 3.44; 95% CI =1.66, 7.14, p value = 0.001). Most participants reported being told about study procedures (95%) and study benefits (98%). Sixty-eight percent of the patients, compared to 47% of the control group reported being told about study risks (p-value <0.001). Of the 165 married women, 19% reported asking permission from their husbands to enroll in the breast cancer study; no one sought permission from local elders. In-depth interviews highlight the use of persuasion and negotiation between a wife and her husband regarding study participation. Conclusions The global expansion of genetic and genomic research highlights our need to understand informed consent practices for studies in ethnically diverse cultural environments such as Africa. Quantitative and qualitative empirical investigations of the informed consent process for genetic and genomic research will further our knowledge of complex issues associated with communication of information, comprehension, decisional authority and voluntary participation. In the future, the development and testing of innovative strategies to promote voluntary participation and comprehension of the goals of genomic research will contribute to our understanding of strategies that enhance the consent process.
    BMC Medical Ethics 05/2014; 15(1):38. DOI:10.1186/1472-6939-15-38 · 1.50 Impact Factor
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    • "There are now many sequencing projects tackling thousands, or tens of thousands of samples; e.g., the UK10K project (http://www.uk10k.org) and the malaria genome consortium [1]. Large sample numbers from both case and control sets are commonly being sequenced in order to detect rare alleles that are associated with disease. "
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    ABSTRACT: A minor but significant fraction of samples subjected to next-generation sequencing methods are either mixed-up or cross-contaminated. These events can lead to false or inconclusive results. We have therefore developed SASI-Seq; a process whereby a set of uniquely barcoded DNA fragments are added to samples destined for sequencing. From the final sequencing data, one can verify that all the reads derive from the original sample(s) and not from contaminants or other samples. By adding a mixture of three uniquely barcoded amplicons, of different sizes spanning the range of insert sizes one would normally use for Illumina sequencing, at a spike-in level of approximately 0.1%, we demonstrate that these fragments remain intimately associated with the sample. They can be detected following even the tightest size selection regimes or exome enrichment and can report the occurrence of sample mix-ups and cross-contamination.As a consequence of this work, we have designed a set of 384 eleven-base Illumina barcode sequences that are at least 5 changes apart from each other, allowing for single-error correction and very low levels of barcode misallocation due to sequencing error. SASI-Seq is a simple, inexpensive and flexible tool that enables sample assurance, allows deconvolution of sample mix-ups and reports levels of cross-contamination between samples throughout NGS workflows.
    BMC Genomics 02/2014; 15(1):110. DOI:10.1186/1471-2164-15-110 · 3.99 Impact Factor
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