Kwiatkowski Group | Natural genetic variation

Kwiatkowski Group | Natural genetic variation

Kwiatkowski Group

Kwiatkowski GroupSanger Institute, Genome Research Limited
Kwiatkowski Group

Our Research and Approach

At the core of malaria biology is a longstanding evolutionary arms race between Plasmodium, Anopheles and human populations. This is still ongoing and has a major impact on disease control efforts. Plasmodium populations are continually evolving to resist antimalarial drugs and to evade the human immune system, while Anopheles populations are continually evolving to resist the insecticides used in vector control. The remarkable ability of both parasite and vector to thwart public health interventions by evolutionary adaptation represents a major obstacle to malaria elimination. The other side of the coin is that malaria has exerted strong selective pressure on the human genome and this has led to natural mechanisms of disease resistance that, if better understood, could provide critical insights into how to develop an effective vaccine.

Our research goal is to gain a deeper understanding of the genetic and molecular mechanisms that underlie these evolutionary processes, and to translate this scientific understanding into actionable knowledge that will lead to more effective and sustainable strategies for disease elimination and vaccine development.

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People

Kwiatkowski, Dominic
Dominic Kwiatkowski
Group Leader

Dominic leads the Malaria Programme at the Sanger Institute.  His own research focuses on using genomics to probe the ongoing evolutionary arms race between parasites, mosquitoes and human populations that are afflicted by malaria, and on translating this knowledge into new strategies for combatting drug and insecticide resistance.

Key Projects, Collaborations, Tools & Data

Dominic Kwiatkowski provides leadership to a number of discreet large-scale collaborations including the MalariaGEN Consortial Projects, Anopheles gambiae 1000 Genomes, Pf3k, and MalariaGEN P. falciparum Community Project, and routinely shares his experience with several other large-scale data-sharing initiatives including the WorldWide Antimalarial Resistance Network (WWARN) and the Plasmodium Diversity Network Africa (PDNA).

Research Programmes

Partners and Funders

Dr Abdoulaye Djimdé is a member of our International Faculty and a leading malaria researcher based in Mali, working primarily on the genetic epidemiology of antimalarial drug resistance in West Africa. He is committed to building research capacity in Africa and has been instrumental in the formation of networks and partnerships collaboratively investigating malaria and drug resistance in the region.The lists below detail our other important partners.
Internal Partners
External Partners and Funders

Publications

  • A novel locus of resistance to severe malaria in a region of ancient balancing selection.

    Malaria Genomic Epidemiology Network, Band G, Rockett KA, Spencer CC and Kwiatkowski DP

    Nature 2015;526;7572;253-7

  • Genetic architecture of artemisinin-resistant Plasmodium falciparum.

    Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J et al.

    Nature genetics 2015;47;3;226-34

  • Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance.

    Mok S, Ashley EA, Ferreira PE, Zhu L, Lin Z et al.

    Science (New York, N.Y.) 2015;347;6220;431-5

  • Reappraisal of known malaria resistance loci in a large multicenter study.

    Malaria Genomic Epidemiology Network and Malaria Genomic Epidemiology Network

    Nature genetics 2014;46;11;1197-204

  • Natural selection and infectious disease in human populations.

    Karlsson EK, Kwiatkowski DP and Sabeti PC

    Nature reviews. Genetics 2014;15;6;379-93

  • A transcriptional switch underlies commitment to sexual development in malaria parasites.

    Kafsack BF, Rovira-Graells N, Clark TG, Bancells C, Crowley VM et al.

    Nature 2014;507;7491;248-52

  • Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.

    Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S et al.

    Nature genetics 2013;45;6;648-55

  • Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.

    Takala-Harrison S, Clark TG, Jacob CG, Cummings MP, Miotto O et al.

    Proceedings of the National Academy of Sciences of the United States of America 2013;110;1;240-5

  • Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

    Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J et al.

    Nature 2012;487;7407;375-9

  • A global network for investigating the genomic epidemiology of malaria.

    Malaria Genomic Epidemiology Network

    Nature 2008;456;7223;732-7

  • Genome-wide and fine-resolution association analysis of malaria in West Africa.

    Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P et al.

    Nature genetics 2009;41;6;657-65

  • Resistance to malaria through structural variation of red blood cell invasion receptors.

    Leffler EM, Band G, Busby GBJ, Kivinen K, Le QS et al.

    Science (New York, N.Y.) 2017

  • Massive introgression drives species radiation at the range limit of Anopheles gambiae.

    Vicente JL, Clarkson CS, Caputo B, Gomes B, Pombi M et al.

    Scientific reports 2017;7;46451

  • Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution.

    Duffy CW, Ba H, Assefa S, Ahouidi AD, Deh YB et al.

    Molecular ecology 2017

  • Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution.

    Rutledge GG, Böhme U, Sanders M, Reid AJ, Cotton JA et al.

    Nature 2017;542;7639;101-104

  • Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study.

    Amato R, Lim P, Miotto O, Amaratunga C, Dek D et al.

    The Lancet. Infectious diseases 2017;17;2;164-173

  • THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites.

    Chang HH, Worby CJ, Yeka A, Nankabirwa J, Kamya MR et al.

    PLoS computational biology 2017;13;1;e1005348

  • Culture adaptation of malaria parasites selects for convergent loss-of-function mutants.

    Claessens A, Affara M, Assefa SA, Kwiatkowski DP and Conway DJ

    Scientific reports 2017;7;41303

  • Micro-epidemiological structuring of Plasmodium falciparum parasite populations in regions with varying transmission intensities in Africa.

    Omedo I, Mogeni P, Bousema T, Rockett K, Amambua-Ngwa A et al.

    Wellcome open research 2017;2;10

  • Whole genome sequencing of Plasmodium falciparum from dried blood spots using selective whole genome amplification.

    Oyola SO, Ariani CV, Hamilton WL, Kekre M, Amenga-Etego LN et al.

    Malaria journal 2016;15;1;597

  • Extreme mutation bias and high AT content in Plasmodium falciparum.

    Hamilton WL, Claessens A, Otto TD, Kekre M, Fairhurst RM et al.

    Nucleic acids research 2016

  • Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi.

    Ravenhall M, Benavente ED, Mipando M, Jensen AT, Sutherland CJ et al.

    Malaria journal 2016;15;1;575

  • Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.

    Srimuang K, Miotto O, Lim P, Fairhurst RM, Kwiatkowski DP et al.

    Malaria journal 2016;15;1;541

  • Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand.

    Auburn S, Serre D, Pearson RD, Amato R, Sriprawat K et al.

    The Journal of infectious diseases 2016;214;8;1235-42

  • Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.

    Hostetler JB, Lo E, Kanjee U, Amaratunga C, Suon S et al.

    PLoS neglected tropical diseases 2016;10;10;e0005091

  • Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum.

    Miles A, Iqbal Z, Vauterin P, Pearson R, Campino S et al.

    Genome research 2016;26;9;1288-99

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

    Pearson RD, Amato R, Auburn S, Miotto O, Almagro-Garcia J et al.

    Nature genetics 2016;48;8;959-64

  • Binding of Plasmodium falciparum Merozoite Surface Proteins DBLMSP and DBLMSP2 to Human Immunoglobulin M Is Conserved among Broadly Diverged Sequence Variants.

    Crosnier C, Iqbal Z, Knuepfer E, Maciuca S, Perrin AJ et al.

    The Journal of biological chemistry 2016;291;27;14285-99

  • Genomic epidemiology of artemisinin resistant malaria.

    MalariaGEN Plasmodium falciparum Community Project

    eLife 2016;5

  • Environmental Correlation Analysis for Genes Associated with Protection against Malaria.

    Mackinnon MJ, Ndila C, Uyoga S, Macharia A, Snow RW et al.

    Molecular biology and evolution 2016

  • The ethics of sustainable genomic research in Africa.

    Parker M and Kwiatkowski DP

    Genome biology 2016;17;1;44

  • A Toll-like receptor-1 variant and its characteristic cellular phenotype is associated with severe malaria in Papua New Guinean children.

    Manning L, Cutts J, Stanisic DI, Laman M, Carmagnac A et al.

    Genes and immunity 2016;17;1;52-9

  • G6PD gene variants and its association with malaria in a Sri Lankan population.

    Dewasurendra RL, Rockett KA, Fernando SD, Carter R, Kwiatkowski DP et al.

    Malaria journal 2015;14;1;603

  • Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae.

    Redmond SN, Eiglmeier K, Mitri C, Markianos K, Guelbeogo WM et al.

    BMC genomics 2015;16;779

  • A novel locus of resistance to severe malaria in a region of ancient balancing selection.

    Malaria Genomic Epidemiology Network, Band G, Rockett KA, Spencer CC and Kwiatkowski DP

    Nature 2015;526;7572;253-7

  • Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study.

    Uyoga S, Ndila CM, Macharia AW, Nyutu G, Shah S et al.

    The Lancet. Haematology 2015;2;10;e437-44

  • K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa.

    Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D et al.

    The Journal of infectious diseases 2015;211;8;1352-5

  • Genetic architecture of artemisinin-resistant Plasmodium falciparum.

    Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J et al.

    Nature genetics 2015;47;3;226-34

  • Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia.

    Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC et al.

    The Journal of infectious diseases 2015;211;5;670-9

  • Malaria genomics: tracking a diverse and evolving parasite population.

    Kwiatkowski D

    International health 2015;7;2;82-4

  • Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance.

    Mok S, Ashley EA, Ferreira PE, Zhu L, Lin Z et al.

    Science (New York, N.Y.) 2015;347;6220;431-5

  • The African Genome Variation Project shapes medical genetics in Africa.

    Gurdasani D, Carstensen T, Tekola-Ayele F, Pagani L, Tachmazidou I et al.

    Nature 2015;517;7534;327-32

  • Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study.

    Roberts Ch, Franklin CS, Makalo P, Joof H, Sarr I et al.

    Scientific reports 2015;5;17447

  • Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

    Shelton JM, Corran P, Risley P, Silva N, Hubbart C et al.

    Malaria journal 2015;14;333

  • Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

    Ocholla H, Preston MD, Mipando M, Jensen AT, Campino S et al.

    The Journal of infectious diseases 2014;210;12;1991-2000

  • Optimized whole-genome amplification strategy for extremely AT-biased template.

    Oyola SO, Manske M, Campino S, Claessens A, Hamilton WL et al.

    DNA research : an international journal for rapid publication of reports on genes and genomes 2014;21;6;661-71

  • Reappraisal of known malaria resistance loci in a large multicenter study.

    Malaria Genomic Epidemiology Network and Malaria Genomic Epidemiology Network

    Nature genetics 2014;46;11;1197-204

  • Monitoring parasite diversity for malaria elimination in sub-Saharan Africa.

    Ghansah A, Amenga-Etego L, Amambua-Ngwa A, Andagalu B, Apinjoh T et al.

    Science (New York, N.Y.) 2014;345;6202;1297-8

  • Spread of artemisinin resistance in Plasmodium falciparum malaria.

    Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P et al.

    The New England journal of medicine 2014;371;5;411-23

  • Adaptive introgression between Anopheles sibling species eliminates a major genomic island but not reproductive isolation.

    Clarkson CS, Weetman D, Essandoh J, Yawson AE, Maslen G et al.

    Nature communications 2014;5;4248

  • Natural selection and infectious disease in human populations.

    Karlsson EK, Kwiatkowski DP and Sabeti PC

    Nature reviews. Genetics 2014;15;6;379-93

  • Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West African populations of differing infection endemicity.

    Mobegi VA, Duffy CW, Amambua-Ngwa A, Loua KM, Laman E et al.

    Molecular biology and evolution 2014;31;6;1490-9

  • Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection.

    Nwakanma DC, Duffy CW, Amambua-Ngwa A, Oriero EC, Bojang KA et al.

    The Journal of infectious diseases 2014;209;7;1126-35

  • Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children.

    Atkinson SH, Uyoga SM, Nyatichi E, Macharia AW, Nyutu G et al.

    Blood 2014;123;13;2008-16

  • A transcriptional switch underlies commitment to sexual development in malaria parasites.

    Kafsack BF, Rovira-Graells N, Clark TG, Bancells C, Crowley VM et al.

    Nature 2014;507;7491;248-52

  • A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Wendler JP, Okombo J, Amato R, Miotto O, Kiara SM et al.

    PloS one 2014;9;5;e96486

  • Detecting and characterizing genomic signatures of positive selection in global populations.

    Liu X, Ong RT, Pillai EN, Elzein AM, Small KS et al.

    American journal of human genetics 2013;92;6;866-81

  • Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.

    Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S et al.

    Nature genetics 2013;45;6;648-55

  • Imputation-based meta-analysis of severe malaria in three African populations.

    Band G, Le QS, Jostins L, Pirinen M, Kivinen K et al.

    PLoS genetics 2013;9;5;e1003509

  • Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria.

    Sundararaman SA, Liu W, Keele BF, Learn GH, Bittinger K et al.

    Proceedings of the National Academy of Sciences of the United States of America 2013;110;17;7020-5

  • The 5q31 region in two African populations as a facet of natural selection by infectious diseases

    Elhassan,A.A.M., Hussein,A.A., Mohamed,H.S., ROCKETT,K., KWIATKOWSKI,D. et al.

    Russian Journal of Genetics 2013;49;2;246-54

  • Efficient depletion of host DNA contamination in malaria clinical sequencing.

    Oyola SO, Gu Y, Manske M, Otto TD, O'Brien J et al.

    Journal of clinical microbiology 2013;51;3;745-51

  • The 5q31 region in two African populations as a facet of natural selection by infectious diseases.

    Elhassan AA, Hussein AA, Mohamed HS, Rockett K, Kwiatkowski D et al.

    Genetika 2013;49;2;279-88

  • A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants.

    Bustamante LY, Bartholdson SJ, Crosnier C, Campos MG, Wanaguru M et al.

    Vaccine 2013;31;2;373-9

  • Effective preparation of Plasmodium vivax field isolates for high-throughput whole genome sequencing.

    Auburn S, Marfurt J, Maslen G, Campino S, Ruano Rubio V et al.

    PloS one 2013;8;1;e53160

  • Human candidate polymorphisms in sympatric ethnic groups differing in malaria susceptibility in Mali.

    Maiga B, Dolo A, Touré O, Dara V, Tapily A et al.

    PloS one 2013;8;10;e75675

  • Bayesian refinement of association signals for 14 loci in 3 common diseases.

    Wellcome Trust Case Control Consortium, Maller JB, McVean G, Byrnes J, Vukcevic D et al.

    Nature genetics 2012;44;12;1294-301

  • Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese.

    Dunstan SJ, Rockett KA, Quyen NT, Teo YY, Thai CQ et al.

    Genes and immunity 2012;13;6;503-8

  • Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

    Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J et al.

    Nature 2012;487;7407;375-9

  • An In-Solution Hybridisation Method for the Isolation of Pathogen DNA from Human DNA-rich Clinical Samples for Analysis by NGS.

    Smith M, Campino S, Gu Y, Clark TG, Otto TD et al.

    The open genomics journal 2012;5

  • Identification of common genetic variation that modulates alternative splicing.

    Hull J, Campino S, Rowlands K, Chan MS, Copley RR et al.

    PLoS genetics 2007;3;6;e99