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Article ; Online: The ethics of sustainable genomic research in Africa.

Parker, Michael / Kwiatkowski, Dominic P

2016 Volume 17, Page(s) 44

Abstract: Michael Parker and Dominic Kwiatkowski discuss important ethical considerations for sustainable genomics research in Africa. ...

Abstract	Michael Parker and Dominic Kwiatkowski discuss important ethical considerations for sustainable genomics research in Africa.
MeSH term(s)	Africa ; Ethics, Research ; Genomics/ethics ; Humans
Language	English
Publishing date	2016-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-016-0914-3
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Article: The ethics of sustainable genomic research in Africa

Parker, Michael / Kwiatkowski, Dominic P

Genome biology. 2016 Dec., v. 17, no. 1

2016

Abstract: Michael Parker and Dominic Kwiatkowski discuss important ethical considerations for sustainable genomics research in Africa. ...

Abstract	Michael Parker and Dominic Kwiatkowski discuss important ethical considerations for sustainable genomics research in Africa.
Keywords	ethics ; genomics ; Africa
Language	English
Dates of publication	2016-12
Size	p. 44.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6906
ISSN (online)	1474-760X
ISSN	1465-6906
DOI	10.1186/s13059-016-0914-3
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Article ; Online: Genomic variation during culture adaptation of genetically complex

Claessens, Antoine / Stewart, Lindsay B / Drury, Eleanor / Ahouidi, Ambroise D / Amambua-Ngwa, Alfred / Diakite, Mahamadou / Kwiatkowski, Dominic P / Awandare, Gordon A / Conway, David J

Microbial genomics

2023 Volume 9, Issue 5

Abstract: Experimental studies on the biology of malaria parasites have mostly been based on laboratory-adapted lines, but there is limited understanding of how these may differ from parasites in natural infections. Loss-of-function mutants have previously been ... ...

Abstract	Experimental studies on the biology of malaria parasites have mostly been based on laboratory-adapted lines, but there is limited understanding of how these may differ from parasites in natural infections. Loss-of-function mutants have previously been shown to emerge during culture of some
MeSH term(s)	Humans ; Plasmodium falciparum/genetics ; Genotype ; Malaria ; Genomics ; Guanine Nucleotide Exchange Factors/genetics ; Protein Serine-Threonine Kinases/genetics
Chemical Substances	Guanine Nucleotide Exchange Factors ; SRPK1 protein, human (EC 2.7.1.-) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-02-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2835258-0
ISSN	2057-5858 ; 2057-5858
ISSN (online)	2057-5858
ISSN	2057-5858
DOI	10.1099/mgen.0.001009
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Article ; Online: Genomics of Plasmodium vivax in Colombia reveals evidence of local bottle-necking and inter-country connectivity in the Americas.

Sutanto, Edwin / Pava, Zuleima / Echeverry, Diego F / Lopera-Mesa, Tatiana M / Montenegro, Lidia Madeline / Yasnot-Acosta, Maria F / Benavente, Ernest Diez / Pearson, Richard D / Herrera, Sócrates / Arévalo-Herrera, Myriam / Trimarsanto, Hidayat / Rumaseb, Angela / Noviyanti, Rintis / Kwiatkowski, Dominic P / Price, Ric N / Auburn, Sarah

Scientific reports

2023 Volume 13, Issue 1, Page(s) 19779

Abstract: Colombia aims to eliminate malaria by 2030 but remains one of the highest burden countries in the Americas. Plasmodium vivax contributes half of all malaria cases, with its control challenged by relapsing parasitaemia, drug resistance and cross-border ... ...

Abstract	Colombia aims to eliminate malaria by 2030 but remains one of the highest burden countries in the Americas. Plasmodium vivax contributes half of all malaria cases, with its control challenged by relapsing parasitaemia, drug resistance and cross-border spread. Using 64 Colombian P. vivax genomes collected between 2013 and 2017, we explored diversity and selection in two major foci of transmission: Chocó and Córdoba. Open-access data from other countries were used for comparative assessment of drug resistance candidates and to assess cross-border spread. Across Colombia, polyclonal infections were infrequent (12%), and infection connectivity was relatively high (median IBD = 5%), consistent with low endemicity. Chocó exhibited a higher frequency of polyclonal infections (23%) than Córdoba (7%), although the difference was not significant (P = 0.300). Most Colombian infections carried double pvdhfr (95%) and single pvdhps (71%) mutants, but other drug resistance mutations were less prevalent (< 10%). There was no evidence of selection at the pvaat1 gene, whose P. falciparum orthologue has recently been implicated in chloroquine resistance. Global population comparisons identified other putative adaptations. Within the Americas, low-level connectivity was observed between Colombia and Peru, highlighting potential for cross-border spread. Our findings demonstrate the potential of molecular data to inform on infection spread and adaptation.
MeSH term(s)	Humans ; Plasmodium vivax/genetics ; Antimalarials/pharmacology ; Colombia/epidemiology ; Malaria, Vivax/epidemiology ; Malaria, Vivax/drug therapy ; Protozoan Proteins/genetics ; Drug Resistance/genetics ; Malaria, Falciparum ; Genomics
Chemical Substances	Antimalarials ; Protozoan Proteins
Language	English
Publishing date	2023-11-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-46076-1
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Article: How malaria has affected the human genome and what human genetics can teach us about malaria.

Kwiatkowski, Dominic P

American journal of human genetics

2005 Volume 77, Issue 2, Page(s) 171–192

Abstract: Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the ... ...

Abstract	Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have arisen in different populations: epidemiological confirmation of the hypotheses that G6PD deficiency, alpha+ thalassemia, and hemoglobin C protect against malaria mortality; the application of novel haplotype-based techniques demonstrating that malaria-protective genes have been subject to recent positive selection; the first genetic linkage maps of resistance to malaria in experimental murine models; and a growing number of reported associations with resistance and susceptibility to human malaria, particularly in genes involved in immunity, inflammation, and cell adhesion. The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine.
MeSH term(s)	Animals ; Biological Evolution ; Disease Models, Animal ; Erythrocytes/cytology ; Family Health ; Genetic Predisposition to Disease ; Genome, Human ; Globins/genetics ; Humans ; Immune System ; Immunity, Innate ; Malaria/epidemiology ; Malaria/genetics ; Mice ; Oxidative Stress ; Plasmodium falciparum
Chemical Substances	Globins (9004-22-2)
Language	English
Publishing date	2005-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1086/432519
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Article: The complexity of genetic variation in a simple immune system.

Kwiatkowski, Dominic P

Trends in genetics : TIG

2005 Volume 21, Issue 4, Page(s) 197–199

Abstract: Fruitflies derived from a wild population vary in their resistance to infection with the bacterial pathogen Serratia marcescens. A survey of nucleotide diversity in 21 genes involved in innate immunity concluded that 16 genes had polymorphisms associated ...

Abstract	Fruitflies derived from a wild population vary in their resistance to infection with the bacterial pathogen Serratia marcescens. A survey of nucleotide diversity in 21 genes involved in innate immunity concluded that 16 genes had polymorphisms associated with resistance to this specific pathogen. However, the effects of individual polymorphisms on the resistance phenotype were modest, and epistatic interactions appeared to be common. What might these findings tell us about genetic resistance to infection in humans?
MeSH term(s)	Animals ; Drosophila/genetics ; Drosophila/immunology ; Drosophila/microbiology ; Evolution, Molecular ; Immunity, Innate/genetics ; Immunity, Innate/immunology ; Polymorphism, Genetic/genetics ; Polymorphism, Genetic/immunology ; Serratia marcescens
Language	English
Publishing date	2005-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2005.02.002
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Article ; Online: Natural selection and infectious disease in human populations.

Karlsson, Elinor K / Kwiatkowski, Dominic P / Sabeti, Pardis C

Nature reviews. Genetics

2014 Volume 15, Issue 6, Page(s) 379–393

Abstract: The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, ... ...

Abstract	The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology.
MeSH term(s)	Communicable Diseases, Emerging/epidemiology ; Communicable Diseases, Emerging/genetics ; Communicable Diseases, Emerging/metabolism ; Humans ; Selection, Genetic
Keywords	covid19
Language	English
Publishing date	2014-04-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2035157-4
ISSN	1471-0064 ; 1471-0056
ISSN (online)	1471-0064
ISSN	1471-0056
DOI	10.1038/nrg3734
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Article ; Online: Malaria outbreak in Laos driven by a selective sweep for Plasmodium falciparum kelch13 R539T mutants: a genetic epidemiology analysis.

Wasakul, Varanya / Disratthakit, Areeya / Mayxay, Mayfong / Chindavongsa, Keobouphaphone / Sengsavath, Viengphone / Thuy-Nhien, Nguyen / Pearson, Richard D / Phalivong, Sonexay / Xayvanghang, Saiamphone / Maude, Richard J / Gonçalves, Sónia / Day, Nicholas P / Newton, Paul N / Ashley, Elizabeth A / Kwiatkowski, Dominic P / Dondorp, Arjen M / Miotto, Olivo

The Lancet. Infectious diseases

2022 Volume 23, Issue 5, Page(s) 568–577

Abstract: Background: Malaria outbreaks are important public health concerns that can cause resurgence in endemic regions approaching elimination. We investigated a Plasmodium falciparum outbreak in Attapeu Province, Laos, during the 2020-21 malaria season, using ...

Abstract	Background: Malaria outbreaks are important public health concerns that can cause resurgence in endemic regions approaching elimination. We investigated a Plasmodium falciparum outbreak in Attapeu Province, Laos, during the 2020-21 malaria season, using genomic epidemiology methods to elucidate parasite population dynamics and identify its causes. Methods: In this genetic analysis, 2164 P falciparum dried blood spot samples were collected from southern Laos between Jan 1, 2017, and April 1, 2021, which included 249 collected during the Attapeu outbreak between April 1, 2020, and April 1, 2021, by routine surveillance. Genetic barcodes obtained from these samples were used to investigate epidemiological changes underpinning the outbreak, estimate population diversity, and analyse population structure. Whole-genome sequencing data from additional historical samples were used to reconstruct the ancestry of outbreak strains using identity-by-descent analyses. Findings: The outbreak parasite populations were characterised by unprecedented loss of genetic diversity, primarily caused by rapid clonal expansion of a multidrug-resistant strain (LAA1) carrying the kelch13 Arg539Thr (R539T) mutation. LAA1 replaced kelch13 Cys580Tyr (C580Y) mutants resistant to dihydroartemisinin-piperaquine (KEL1/PLA1) as the dominant strain. LAA1 inherited 58·8% of its genome from a strain circulating in Cambodia in 2008. A secondary outbreak strain (LAA2) carried the kelch13 C580Y allele, and a genome that is essentially identical to a Cambodian parasite from 2009. A third, low-frequency strain (LAA7) was a recombinant of KEL1/PLA1 with a kelch13 R539T mutant. Interpretation: These results strongly suggest that the outbreak was driven by a selective sweep, possibly associated with multidrug-resistant phenotypes of the outbreak strains. Established resistant populations can circulate at low frequencies for years before suddenly overwhelming dominant strains when the conditions for selection become favourable-eg, when front-line therapies change. Genetic surveillance can support elimination by characterising key properties of outbreaks such as population diversity, drug resistance marker prevalence, and the origins of outbreak strains. Funding: Bill & Melinda Gates Foundation; The Global Fund to Fight AIDS, Tuberculosis and Malaria; Wellcome Trust. Translation: For the Lao translation of the abstract see Supplementary Materials section.
MeSH term(s)	Humans ; Plasmodium falciparum/genetics ; Laos/epidemiology ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Malaria, Falciparum/drug therapy ; Molecular Epidemiology ; Drug Resistance/genetics ; Malaria/epidemiology ; Disease Outbreaks ; Protozoan Proteins/genetics ; Protozoan Proteins/therapeutic use
Chemical Substances	Antimalarials ; Protozoan Proteins
Language	English
Publishing date	2022-11-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00697-1
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Article ; Online: LookSeq: a browser-based viewer for deep sequencing data.

Manske, Heinrich Magnus / Kwiatkowski, Dominic P

Genome research

2009 Volume 19, Issue 11, Page(s) 2125–2132

Abstract: Sequencing a genome to great depth can be highly informative about heterogeneity within an individual or a population. Here we address the problem of how to visualize the multiple layers of information contained in deep sequencing data. We propose an ... ...

Abstract	Sequencing a genome to great depth can be highly informative about heterogeneity within an individual or a population. Here we address the problem of how to visualize the multiple layers of information contained in deep sequencing data. We propose an interactive AJAX-based web viewer for browsing large data sets of aligned sequence reads. By enabling seamless browsing and fast zooming, the LookSeq program assists the user to assimilate information at different levels of resolution, from an overview of a genomic region to fine details such as heterogeneity within the sample. A specific problem, particularly if the sample is heterogeneous, is how to depict information about structural variation. LookSeq provides a simple graphical representation of paired sequence reads that is more revealing about potential insertions and deletions than are conventional methods.
MeSH term(s)	Algorithms ; Animals ; Base Sequence ; Databases, Nucleic Acid ; Genetic Variation ; Genome, Protozoan/genetics ; Genomics/methods ; Humans ; Information Storage and Retrieval/methods ; Internet ; Molecular Sequence Data ; Plasmodium falciparum/genetics ; Sequence Alignment/methods ; Sequence Homology, Nucleic Acid ; Software
Language	English
Publishing date	2009-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.093443.109
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Article ; Online: Whole-genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes.

Lucas, Eric R / Miles, Alistair / Harding, Nicholas J / Clarkson, Chris S / Lawniczak, Mara K N / Kwiatkowski, Dominic P / Weetman, David / Donnelly, Martin J

Genome research

2019 Volume 29, Issue 8, Page(s) 1250–1261

Abstract: Polymorphisms in genetic copy number can influence gene expression, coding sequence, and zygosity, making them powerful actors in the evolutionary process. Copy number variants (CNVs) are however understudied, being more difficult to detect than single- ... ...

Abstract	Polymorphisms in genetic copy number can influence gene expression, coding sequence, and zygosity, making them powerful actors in the evolutionary process. Copy number variants (CNVs) are however understudied, being more difficult to detect than single-nucleotide polymorphisms. We take advantage of the intense selective pressures on the major malaria vector
MeSH term(s)	Animals ; Anopheles/genetics ; Anopheles/parasitology ; Biological Evolution ; Chromosome Mapping ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; DNA Copy Number Variations ; Gene Dosage ; Genetic Loci ; Genome, Insect ; Haplotypes ; Homozygote ; Humans ; Insect Proteins/genetics ; Insect Proteins/metabolism ; Insecticide Resistance/genetics ; Insecticides ; Malaria/prevention & control ; Malaria/transmission ; Mosquito Vectors/genetics ; Mosquito Vectors/parasitology ; Multigene Family ; Pyrethrins ; Selection, Genetic ; Whole Genome Sequencing
Chemical Substances	Insect Proteins ; Insecticides ; Pyrethrins ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2019-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.245795.118
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