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4 results on '"Hubbart C"'

1. Genomic analysis of local variation and recent evolution in Plasmodium vivax.

Author

Pearson RD, Amato R, Auburn S, Miotto O, Almagro-Garcia J, Amaratunga C, Suon S, Mao S, Noviyanti R, Trimarsanto H, Marfurt J, Anstey NM, William T, Boni MF, Dolecek C, Hien TT, White NJ, Michon P, Siba P, Tavul L, Harrison G, Barry A, Mueller I, Ferreira MU, Karunaweera N, Randrianarivelojosia M, Gao Q, Hubbart C, Hart L, Jeffery B, Drury E, Mead D, Kekre M, Campino S, Manske M, Cornelius VJ, MacInnis B, Rockett KA, Miles A, Rayner JC, Fairhurst RM, Nosten F, Price RN, and Kwiatkowski DP

Subjects
Humans, Malaria, Vivax parasitology, Malaria, Vivax transmission, Plasmodium vivax pathogenicity, Biological Evolution, Genetic Markers genetics, Genetic Variation genetics, Genomics methods, Malaria, Vivax genetics, Plasmodium vivax genetics
Abstract

The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax., Competing Interests: The authors declare no competing financial interests.

Published
2016
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2. Genome-wide and fine-resolution association analysis of malaria in West Africa

Author

Muminatou, Jallow, Yik Ying Teo, Small, Kerrin S., Rockett, Kirk A., Panos, Deloukas, Clark, Taane G., Katja, Kivinen, Bojang, Kalifa A., Conway, David J., Margaret, Pinder, Giorgio, Sirugo, Fatou Sisay Joof, Stanley, Usen, Sarah, Auburn, Bumpstead, Suzannah J., Susana, Campino, Alison, Coffey, Andrew, Dunham, Fry, Andrew E., Angela, Green, Rhian, Gwilliam, Hunt, Sarah E., Michael, Inouye, Jeffreys, Anna E., Alieu, Mendy, Aarno, Palotie, Simon, Potter, Jiannis, Ragoussis, Jane, Rogers, Kate, Rowlands, Elilan, Somaskantharajah, Pamela, Whittaker, Claire, Widden, Peter, Donnelly, Bryan, Howie, Jonathan, Marchini, Andrew, Morris, Miguel, Sanjoaquin, Eric Akum Achidi, Tsiri, Agbenyega, Angela, Allen, Olukemi, Amodu, Patrick, Corran, Abdoulaye, Djimde, Amagana, Dolo, Doumbo, Ogobara K., Chris, Drakeley, Sarah, Dunstan, Jennifer, Evans, Jeremy, Farrar, Hien Tt, Fernando D., Horstmann, R. D., Ibrahim, M., Karunaweera, N., Kokwaro, G., Koram, K. A., Lemnge, M., Makani, J., Marsh, K., Michon, P., David, Modiano, Molyneux, M. E., Mueller, I., Parker, M., Peshu, N., Plowe, C. V., Puijalon, O., Reeder, J., Reyburn, H., Riley, E. M., Sakuntabhai, A., Singhasivanon, P., Sirima, S., Tall, A., Taylor, T. E., Thera, M., Troye Blomberg, M., Williams, T. N., Wilson, M., Wellcome Trust Case Control Consortium Kwiatkowski, D. P., Epidemiology Network: Achidi, Malaria Genomic E. A., Agbenyega, T., Ahmad, T., Alcock, D., Allen, S., Amenga Etego, L., Amodu, O., Apinjoh, T. O., Attwood, A. P., Auburn, S., Ball, S. G., Balmforth, A. J., Ban, M., Barbour, J., Barnwell, D., Barrett, J. C., Barrett, J. H., Barton, A., Bentley, D., Bishop, D. T., Bojang, K., Boorman, J. P., Bougouma, E., Bradbury, L. A., Braga Marcano, C. A., Braund, P. S., Bredin, F., Breen, G., Brown, M. A., Brown, M. J., Bruce, I. N., Bryan, C., Bull, S., Bumpstead, S. J., Burke, B., Burton, P. R., Caesar, S., Campino, S., Cant, B., Cardin, N. J., Cardon, L. R., Carucci, D., Caulfield, M., Chaney, A., Clark, T., Clayton, D. G., Collier, D. A., Compston, A., Compston, D. A., Connell, J., Conway, D., Cook, K., Corran, P., Craddock, N., Cummings, F. R., Davison, D., Deloukas, P., Devries, J., Dewasurendra, R., Diakite, M., Dixon, R. J., Djimde, A., Dobson, R., Dolo, A., Dominiczak, A., Donnelly, P., Donovan, H., Doumbo, O., Downes, K., Doyle, A., Drakeley, C., Drummond, H., Duffy, P., Duncanson, A., Dunger, D. B., Dunstan, S., Duombo, O., Easton, D., Elkin, A., Elliott, K. S., Elzein, A., Enimil, A., Evans, D., Evans, J., Everson, U., Eyre, S., Farmer, A., Farrall, M., Farrar, C., Farrar, J., Fernando, D., Ferreira, T., Ferrier, I. N., Fisher, S. A., Fitzpatrick, K., Forbes, A., Franklyn, J. A., Fraser, C., Frayling, T. M., Freathy, R. M., Ghansah, A., Ghori, J., Gilbert, P. D., Gordon Smith, K., Goris, A., Gottlieb, M., Gough, S. C., Green, A., Green, E. K., Groves, C. J., Grozeva, D., Gungadoo, J., Gwilliam, R., Hall, A. S., Hallgrimsdóttir, I. B., Hamshere, M. L., Hart, L., Hattersley, A. T., Heward, J. M., Hider, S. L., Tran Tinh Hien, Hill, A. V., Hilton, E., Hinks, A. M., Hitman, G. A., Holmans, P. A., Horstmann, Rolf D., Howie, B. N., Hubbart, C., Hughes, C., Hunt, S. E., Hussein, A., Hussey, J. M., Muntaser, Ibrahim, Iles, M. M., Inouye, M., Ishengoma, D., Jallow, M., Jeffreys, A. E., Jewell, D. P., John, Sl, Jolley, J. D., Jones, I. R., Jones, L., Jones, R. W., Nadira, Karunaweera, Keniry, A., King, E., Kirov, G., Kivinen, K., Knight, A. S., Koch, K., Gilbert, Kokwaro, Koram, Kwadwo A., Lango, H., Lathrop, G. M., Lee, K. L., Lees, C. W., Martha, Lemnge, Leung, H. T., Lewis, C. M., Lin, E., Lindgren, C. M., Ly, A., Macinnis, B., Julie, Makani, Mangano, Valentina, Mangino, M., Manjurano, A., Manning, L., Mansfield, J. C., Manske, M., Maqbool, A., Marchini, J. L., Kevin, Marsh, Maslen, G., Mathew, C. G., Mcardle, W. L., Mccarthy, M. I., Mccreight, M., Mcginnis, R., Mcguffin, P., Meech, E., Mendy, A., Pascal, Michon, Mohiuddin, M. K., Molyneux, Malcolm E., Morris, A. P., Moskvina, V., Moyes, C., Ivo, Mueller, Munroe, P. B., Mutabingwa, T., Ndila, C. M., Newhouse, S. J., Newport, M., Nikolov, I., Nimmo, E. R., Nutland, S., Nyirongo, V., O'Donovan, M. C., Oluoch, T., Onipinla, A., Onnie, C. M., Ouwehand, W. H., Owen, M. J., Michael, Parker, Parkes, M., Pembrey, M., Pereira Gale, J., Perry, J. R., Norbert, Peshu, Plowe, Christopher V., Pointon, J. J., Potter, C., Potter, S., Prescott, N. J., Prowse, C. V., Odile, Puijalon, Quyen, N. T., Ragoussis, J., Rahman, N., Ravindrarajah, R., Rayner, N. W., John, Reeder, Hugh, Reyburn, Riley, Eleanor M., Ring, S. M., Risley, P., Rockett, K. A., Rogers, J., Rowlands, K., Anavaj, Sakuntabhai, Samani, N. J., Sanderson, J., Sanjoaquin, M., Satsangi, J., Sawcer, S. J., Seal, S., Shields, B. M., Silman, A. J., Simmonds, M. J., Pratap, Singhasivanon, Sodiomon, Sirima, Sirugo, G., Small, K. S., Somaskantharajah, E., Spencer, C. C., St Clair, D., Stevens, H. E., Stevens, M., Stevens, S., Strachan, D. P., Stratton, M. R., Su, Z., Suriyaphol, P., Symmons, D. P., Adama, Tall, Taylor, N. C., Taylor, Terrie E., Teo, Y., Teo, Y. Y., Mahamadou, Thera, Thompson, J. R., Thomson, W., Timpson, N. J., Tobin, M. D., Todd, J. A., Todhunter, C. E., Toure, O., Tremelling, M., Marita Troye Blomberg, Vanderwal, A., Vukcevic, D., Walker, M., Walker, N. M., Wallace, C., Walters, G. R., Walton, R., Watkins, N. A., Watson, R., Webster, J., Weedon, M. N., Whittaker, P., Widmer, B., Williams, Thomas N., Williamson, R., Michael, Wilson, Winzer, T., Withers, D., Wordsworth, P., Worthington, J., Wrigley, R., Xue, M., Young, A. H., Yuldasheva, N., and Zeggini, E.

Subjects
Linkage disequilibrium, Hemoglobin, Sickle, Population, Genome-wide association study, Locus (genetics), Biology, Population stratification, Polymorphism, Single Nucleotide, Severity of Illness Index, Linkage Disequilibrium, Article, Gene mapping, Reference Values, Ethnicity, Genetics, Humans, education, Genetic association, education.field_of_study, Polymorphism, Genetic, Chromosome Mapping, Genetic Variation, Malaria, Gambia, Imputation (genetics), Genome-Wide Association Study
Abstract

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.

Published
2009

3. Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya

Author

Shah, S, Macharia, A, Makale, J, Uyoga, S, Kivinen, K, Craik, R, Hubbart, C, Wellems, T, Rockett, K, Kwiatkowski, D, and Williams, T

Subjects
Male, Heterozygote, Erythrocytes, Genotype, Chromosome Mapping, Genetic Variation, Infant, Sequence Analysis, DNA, Glucosephosphate Dehydrogenase, Kenya, Polymorphism, Single Nucleotide, Malaria, Cohort Studies, Glucosephosphate Dehydrogenase Deficiency, Haplotypes, Genetic Loci, G6PD deficiency, Genetics, Odds Ratio, Humans, Genetics(clinical), Female, Alleles, Research Article
Abstract

Background: The relationship between glucose-6-phosphate dehydrogenase (G6PD) deficiency and clinical phenomena such as primaquine-sensitivity and protection from severe malaria remains poorly defined, with past association studies yielding inconsistent and conflicting results. One possibility is that examination of a single genetic variant might underestimate the presence of true effects in the presence of unrecognized functional allelic diversity. Methods: We systematically examined this possibility in Kenya, conducting a fine-mapping association study of erythrocyte G6PD activity in 1828 Kenyan children across 30 polymorphisms at or around the G6PD locus. Results: We demonstrate a strong functional role for c.202G>A (rs1050828), which accounts for the majority of variance in enzyme activity observed (P=1.5 × 10-200, additive model). Additionally, we identify other common variants that exert smaller, intercorrelated effects independent of c.202G>A, and haplotype analyses suggest that each variant tags one of two haplotype motifs that are opposite in sequence identity and effect direction. We posit that these effects are of biological and possible clinical significance, specifically noting that c.376A>G (rs1050829) augments 202AG heterozygote risk for deficiency trait by two-fold (OR = 2.11 [1.12 - 3.84], P=0.014). Conclusions: Our results suggest that c.202G>A is responsible for the majority of the observed prevalence of G6PD deficiency trait in Kenya, but also identify a novel role for c.376A>G as a genetic modifier which marks a common haplotype that augments the risk conferred to 202AG heterozygotes, suggesting that variation at both loci merits consideration in genetic association studies probing G6PD deficiency-associated clinical phenotypes.

Published
2014

4. Admixture into and within sub-Saharan Africa

Author

Angeliki Kerasidou, J O'Brien, Aaron Vanderwal, Christina Hubbart, Alistair Miles, Catherine L. Moyes, A Nyika, Abier Elzein, J Shelton, Spencer Cca., Anthony Enimil, A Diss, C Hughes, Lucas Amenga-Etego, E Somaskantharajah, Ogobara K. Doumbo, Jacob Almagro Garcia, Valentina D. Mangano, E Drury, Edith Bougama, Angie Green, Busby Gbj., Geraldine M. Clarke, Dominic P. Kwiatkowski, Jiannis Ragoussis, Alphaxard Manjurano, Bronwyn MacInnis, Tobias O. Apinjoh, D Mead, Gareth Maslen, George B.J. Busby, Kirk A. Rockett, Dushyanth Jyothi, C Potter, C Malangone, Muminatou Jallow, I Ragoussis, Ellen M. Leffler, J Rogers, J Stalker, Quang Si Le, J Rodford, D Barnwell, Alieu Mendy, J deVries, Anna E. Jeffreys, Carolyne M. Ndila, E Hilton, Vysaul Nyirongo, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], The Wellcome Trust Sanger Institute [Cambridge], Medical Research Council Unit The Gambia (MRC), Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Navrongo Health Research Centre [Navrongo, Ghana] (NHRC), Komfo Anokye Teaching Hospital, University of Buéa, KEMRI-Wellcome Trust Research Programme (KWTRP), London School of Hygiene and Tropical Medicine (LSHTM), University of Malawi, University of Bamako [Mali], Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Wellcome Trust, Medical Research Council, Foundation for the National Institutes of Health, Malaria Genomics Epidemiology Network : Vanderwal A, Elzein A, Nyika A, Mendy A, Miles A, Diss A, Kerasidou A, Green A, Jeffreys AE, MacInnis B, Hughes C, Moyes C, Spencer CC, Hubbart C, Malangone C, Potter C, Mead D, Barnwell D, Kwiatkowski DP, Jyothi D, Drury E, Somaskantharajah E, Hilton E, Leffler E, Maslen G, Band G, Busby G, Clarke GM, Ragoussis I, Garcia JA, Rogers J, deVries J, Shelton J, Ragoussis J, Stalker J, Rodford J, O'Brien J, Evans J, Rowlands K, Cook K, Fitzpatrick K, Kivinen K, Small K, Johnson KJ, Rockett KA, Hart L, Manske M, McCreight M, Stevens M, Pirinen M, Hennsman M, Parker M, SanJoaquin M, Seplúveda N, Cook O, Miotto O, Deloukas P, Craik R, Wrigley R, Watson R, Pearson R, Hutton R, Oyola S, Auburn S, Shah S, Le SQ, Molloy S, Bull S, Campino S, Clark TG, Ruano-Rubio V, Cornelius V, Teo YY, Corran P, Silva ND, Risley P, Doyle A, Evans J, Horstmann R, Plowe C, Duffy P, Carucci D, Gottleib M, Tall A, Ly AB, Dolo A, Sakuntabhai A, Puijalon O, Bah A, Camara A, Sadiq A, Khan AA, Jobarteh A, Mendy A, Ebonyi A, Danso B, Taal B, Casals-Pascual C, Conway DJ, Onykwelu E, Sisay-Joof F, Sirugo G, Kanyi H, Njie H, Obu H, Saine H, Sambou I, Abubakar I, Njie J, Fullah J, Jaiteh J, Bojang KA, Jammeh K, Sabally-Ceesay K, Manneh L, Camara L, Yamoah L, Njie M, Njie M, Pinder M, Jallow M, Aiyegbo M, Jasseh M, Keita ML, Saidy-Khan M, Jallow M, Ceesay N, Rasheed O, Ceesay PL, Esangbedo P, Cole-Ceesay R, Olaosebikan R, Correa S, Njie S, Usen S, Dibba Y, Barry A, Djimdé A, Sall AH, Abathina A, Niangaly A, Dembele A, Poudiougou B, Diarra E, Bamba K, Thera MA, Doumbo O, Toure O, Konate S, Sissoko S, Diakite M, Konate AT, Modiano D, Bougouma EC, Bancone G, Ouedraogo IN, Simpore J, Sirima SB, Mangano VD, Troye-Blomberg M, Oduro AR, Hodgson AV, Ghansah A, Nkrumah F, Atuguba F, Koram KA, Amenga-Etego LN, Wilson MD, Ansah NA, Mensah N, Ansah PA, Anyorigiya T, Asoala V, Rogers WO, Akoto AO, Ofori AO, Enimil A, Ansong D, Sambian D, Asafo-Agyei E, Sylverken J, Antwi S, Agbenyega T, Orimadegun AE, Amodu FA, Oni O, Omotade OO, Amodu O, Olaniyan S, Ndi A, Yafi C, Achidi EA, Mbunwe E, Anchang-Kimbi J, Mugri R, Besingi R, Apinjoh TO, Titanji V, Elhassan A, Hussein A, Mohamed H, Elhassan I, Ibrahim M, Kokwaro G, Oluoch T, Macharia A, Ndila CM, Newton C, Opi DH, Kamuya D, Bauni E, Marsh K, Peshu N, Molyneux S, Uyoga S, Williams TN, Marsh V, Manjurano A, Nadjm B, Maxwell C, Drakeley C, Riley E, Mtei F, Mtove G, Wangai H, Reyburn H, Joseph S, Ishengoma D, Lemnge M, Mutabingwa T, Makani J, Cox S, Phiri A, Munthali A, Kachala D, Njiragoma L, Molyneux ME, Moore M, Ntunthama N, Pensulo P, Taylor T, Nyirongo V, Carter R, Fernando D, Karunaweera N, Dewasurendra R, Suriyaphol P, Singhasivanon P, Simmons CP, Thai CQ, Sinh DX, Farrar J, Chuong LV, Phu NH, Hieu NT, Hoang Mai NT, Ngoc Quyen NT, Day N, Dunstan SJ, O'Riordan SE, Hong Chau TT, Hien TT, Allen A, Lin E, Karunajeewa H, Mueller I, Reeder J, Manning L, Laman M, Michon P, Siba P, Allen S, Davis TM., Commission of the European Communities, and Wellcome Trust

Subjects
0301 basic medicine, Population genetics, Gene flow, 0302 clinical medicine, MESH: Genetic Variation, Biology (General), African Continental Ancestry Group, media_common, Genetics, 0303 health sciences, education.field_of_study, Human migration, General Neuroscience, 030305 genetics & heredity, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Geography, Genomics and Evolutionary Biology, MESH: Human Migration, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, admixture, gene-flow, Research Article, Gene Flow, QH301-705.5, Science, media_common.quotation_subject, Human Migration, Population, Black People, Genomics, Biology, africa, chromosome painting, evolutionary biology, genomics, human, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Genetic variation, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Africa South of the Sahara, Allele, education, Africa South of the Sahara, MESH: Gene Flow, MESH: Genome, Human, 030304 developmental biology, Genetic diversity, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], General Immunology and Microbiology, business.industry, Genome, Human, Haplotype, Genetic Variation, MESH: Haplotypes, 030104 developmental biology, Genetic epidemiology, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Agriculture, Evolutionary biology, Africa, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: African Continental Ancestry Group, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, 030217 neurology & neurosurgery, Demography, Diversity (politics)
Abstract

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology. DOI: http://dx.doi.org/10.7554/eLife.15266.001, eLife digest Our genomes contain a record of historical events. This is because when groups of people are separated for generations, the DNA sequence in the two groups’ genomes will change in different ways. Looking at the differences in the genomes of people from the same population can help researchers to understand and reconstruct the historical interactions that brought their ancestors together. The mixing of two populations that were previously separate is known as admixture. Africa as a continent has few written records of its history. This means that it is somewhat unknown which important movements of people in the past generated the populations found in modern-day Africa. Busby et al. have now attempted to use DNA to look into this and reconstruct the last 4000 years of genetic history in African populations. As has been shown in other regions of the world, the new analysis showed that all African populations are the result of historical admixture events. However, Busby et al. could characterize these events to unprecedented level of detail. For example, multiple ethnic groups from The Gambia and Mali all show signs of sharing the same set of ancestors from West Africa, Europe and Asia who mixed around 2000 years ago. Evidence of a migration of people from Central West Africa, known as the Bantu expansion, could also be detected, and was shown to carry genes to the south and east. An important next step will be to now look at the consequences of the observed gene-flow, and ask if it has contributed to spreading beneficial, or detrimental, mutations around Africa. DOI: http://dx.doi.org/10.7554/eLife.15266.002

Published
2016

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