期刊
NATURE GENETICS
卷 45, 期 6, 页码 648-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2624
关键词
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资金
- Wellcome Trust through core funding of the Wellcome Trust Sanger Institute [098051]
- Wellcome Trust through core funding of the Wellcome Trust Centre for Human Genetics [090532/Z/09/Z]
- Wellcome Trust through a Strategic Award [090770/Z/09/Z]
- MRC through the MRC Centre for Genomics and Global Health [G0600718]
- MRC through an MRC Professorship [G19/9]
- Wellcome Trust
- MRC
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health
- Howard Hughes Medical Institute International Scholarship [55005502]
- Medical Research Council [MC_EX_MR/K02440X/1, 1252410, G0600718, MC_U190081987, G19/9] Funding Source: researchfish
- MRC [MC_EX_MR/K02440X/1, G19/9, MC_U190081987, G0600718] Funding Source: UKRI
We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
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