Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies.
Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies.
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DOI：
10.1186/1471-2156-11-65
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发表时间：
2010-07-13
期刊：
影响因子：
2.9
通讯作者：
Ferreira MU
中科院分区：
文献类型：
--
作者：
Orjuela-Sánchez P;Karunaweera ND;da Silva-Nunes M;da Silva NS;Scopel KK;Gonçalves RM;Amaratunga C;Sá JM;Socheat D;Fairhust RM;Gunawardena S;Thavakodirasah T;Galapaththy GL;Abeysinghe R;Kawamoto F;Wirth DF;Ferreira MU
通过全基因组关联研究，用于初步绘制有助于表型（如耐药性和毒力）的基因组区域的理想疟疾寄生虫种群是具有高遗传多样性的种群，允许许多信息标记，以及罕见的减数分裂重组，允许标记和表型决定基因座之间的强连锁不平衡（LD）。然而，主要的人类疟疾寄生虫间日疟原虫的田间种群的遗传多样性和LD水平仍然很少表征。我们检查了238个来自南美洲和亚洲低至中度疟疾流行地区的间日疟原虫田间分离株的100 kb染色体片段上的单核苷酸多态性（SNP）和LD模式，其中LD往往比全流行人群更广泛，以及两种猴子适应株（萨尔瓦多-I，来自萨尔瓦多萨尔瓦多和贝伦，来自巴西）。我们发现不同水平的SNP多样性和LD在人群中，最高的多样性和最强的LD在疟疾传播最低的地区。我们发现了几个集群的连续标记与罕见的减数分裂重组，其特点是一个相对保守的单倍型结构之间的人口，这表明存在重组热点的基因组区域分析。沉默和非同义SNPs揭示了大量的种群间分化，占观察到的总体遗传多样性的约40%。尽管寄生虫根据其大陆起源聚集，但我们发现了巴西间日疟原虫种群内部亚结构的证据。我们还探讨了受自然选择影响的pvmdr-1基因座核苷酸替换频率的明显地理变异，pvmdr-1基因座与耐药性相关。这些发现支持了在精心选择的间日疟原虫种群中使用相对低密度的标记进行全基因组关联研究的可行性，但强调了在地方和区域水平上由种群结构引起的假阳性风险。见评注：http://www.biomedcentral.com/1741-7007/8/90
The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for ~40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels. See commentary: http://www.biomedcentral.com/1741-7007/8/90
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影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
5.4
作者：
HILL W G;ROBERTSON A
通讯作者：
ROBERTSON A
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
16
作者：
Fidock, DA;Nomura, T;Wellems, TE
通讯作者：
Wellems, TE
DOI：
10.4269/ajtmh.2009.09-0042
发表时间：
2009-11-01
影响因子：
3.3
作者：
Fernando, S. Deepika;Abeyasinghe, Rabindra R.;Rajapaksa, Lalani C.
通讯作者：
Rajapaksa, Lalani C.