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Genome variation and meiotic recombination in Plasmodium falciparum: insights from deep sequencing of genetic crosses

Alistair Miles, Zamin Iqbal, Paul Vauterin, Richard Pearson, Susana Campino, Michel Theron, Kelda Gould, Daniel Mead, Eleanor Drury, John O’Brien, Valentin Ruano Rubio, Bronwyn Macinnis, Jonathan Mwangi, Upeka Samarakoon, Lisa Ranford-Cartwright, Michael Ferdig, Karen Hayton, Xinzhuan Su, Thomas Wellems, Julian Rayner, Gil McVean, Dominic Kwiatkowski
doi: https://doi.org/10.1101/024182
Alistair Miles
1MRC Centre for Genomics and Global Health, University of Oxford, Oxford, UK
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Zamin Iqbal
3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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Paul Vauterin
1MRC Centre for Genomics and Global Health, University of Oxford, Oxford, UK
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Richard Pearson
1MRC Centre for Genomics and Global Health, University of Oxford, Oxford, UK
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Susana Campino
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Michel Theron
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Kelda Gould
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Daniel Mead
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Eleanor Drury
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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John O’Brien
4Bowdoin College, Brunswick, Maine, USA
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Valentin Ruano Rubio
5Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
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Bronwyn Macinnis
5Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
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Jonathan Mwangi
6Department of Biochemistry, Medical School, Mount Kenya University, General Kago Road, Thika, Kenya
7Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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Upeka Samarakoon
8Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA
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Lisa Ranford-Cartwright
7Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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Michael Ferdig
8Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA
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Karen Hayton
9Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA
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Xinzhuan Su
9Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA
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Thomas Wellems
9Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA
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Julian Rayner
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
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Gil McVean
3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
10Department of Statistics, University of Oxford, Oxford, UK
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Dominic Kwiatkowski
2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, UK
1MRC Centre for Genomics and Global Health, University of Oxford, Oxford, UK
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Abstract

The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of parasite evolution is impeded by the fact that a large fraction of the genome is either highly repetitive or highly variable, and thus difficult to analyse using short read technologies. Here we describe a resource of deep sequencing data on parents and progeny from genetic crosses, which has enabled us to perform the first integrated analysis of SNP, INDEL and complex polymorphisms, using Mendelian error rates as an indicator of genotypic accuracy. These data reveal that INDELs are exceptionally abundant and the dominant mode of polymorphism within the core genome. We analyse patterns of meiotic recombination, including the relative contribution of crossover and non-crossover events, and we observe several instances of recombination that modify copy number variants associated with drug resistance. We describe a novel web application that allows these data to be explored in detail.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 07, 2015.
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Genome variation and meiotic recombination in Plasmodium falciparum: insights from deep sequencing of genetic crosses
Alistair Miles, Zamin Iqbal, Paul Vauterin, Richard Pearson, Susana Campino, Michel Theron, Kelda Gould, Daniel Mead, Eleanor Drury, John O’Brien, Valentin Ruano Rubio, Bronwyn Macinnis, Jonathan Mwangi, Upeka Samarakoon, Lisa Ranford-Cartwright, Michael Ferdig, Karen Hayton, Xinzhuan Su, Thomas Wellems, Julian Rayner, Gil McVean, Dominic Kwiatkowski
bioRxiv 024182; doi: https://doi.org/10.1101/024182
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Genome variation and meiotic recombination in Plasmodium falciparum: insights from deep sequencing of genetic crosses
Alistair Miles, Zamin Iqbal, Paul Vauterin, Richard Pearson, Susana Campino, Michel Theron, Kelda Gould, Daniel Mead, Eleanor Drury, John O’Brien, Valentin Ruano Rubio, Bronwyn Macinnis, Jonathan Mwangi, Upeka Samarakoon, Lisa Ranford-Cartwright, Michael Ferdig, Karen Hayton, Xinzhuan Su, Thomas Wellems, Julian Rayner, Gil McVean, Dominic Kwiatkowski
bioRxiv 024182; doi: https://doi.org/10.1101/024182

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