Diversity, differentiation, and linkage disequilibrium: prospects for association mapping in the malaria vector Anopheles arabiensis.
Diversity, differentiation, and linkage disequilibrium: prospects for association mapping in the malaria vector Anopheles arabiensis.
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DOI：
10.1534/g3.113.008326
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发表时间：
2014-01-10
期刊：
影响因子：
--
通讯作者：
Lanzaro GC
中科院分区：
文献类型：
--
作者：
Marsden CD;Lee Y;Kreppel K;Weakley A;Cornel A;Ferguson HM;Eskin E;Lanzaro GC
关联作图是阐明表型性状遗传基础的一种广泛应用的方法。然而，连锁不平衡和遗传多样性水平等因素会影响这种方法的能力和分辨率。此外，如果不考虑样本之间的总体细分，可能会导致虚假关联。因此，在进行关联映射实验之前，对这些因素有一个详细的了解是有用的。在这里，我们对24个疟疾媒介阿拉伯按蚊的标本进行了全基因组测序，以进一步了解该物种的遗传多样性、种群细分和连锁不平衡的模式。我们在AN中发现了高水平的遗传多样性。阿拉伯基因组，检测到约80万个高置信度、单核苷酸多态。然而，核苷酸多样性水平在染色体内和染色体之间都有很大的差异。我们观察到X染色体、一些倒位和着丝粒附近的多样性较低。在当地(坦桑尼亚的基隆贝罗河谷)没有种群结构，但在遥远的种群(喀麦隆和坦桑尼亚)之间发现了种群结构，这些种群的分化在很大程度上限于某些常染色体倒位，如2RB。总体而言，内部的链接不平衡。阿拉比虫在所有染色体上迅速腐烂(在200个碱基对以内)。然而，在一些倒位中观察到了升高的连锁不平衡，这表明这些区域的重组减少了。连锁不平衡的总体水平很低，这表明除了大效应的变种外，在这个分类群中的关联性研究将是非常具有挑战性的，并且将需要大样本量。
Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples can result in spurious associations if not accounted for. As such, it is useful to have a detailed understanding of these factors before conducting association mapping experiments. Here we conducted whole-genome sequencing on 24 specimens of the malaria mosquito vector, Anopheles arabiensis, to further understanding of patterns of genetic diversity, population subdivision and linkage disequilibrium in this species. We found high levels of genetic diversity within the An. arabiensis genome, with ~800,000 high-confidence, single- nucleotide polymorphisms detected. However, levels of nucleotide diversity varied significantly both within and between chromosomes. We observed lower diversity on the X chromosome, within some inversions, and near centromeres. Population structure was absent at the local scale (Kilombero Valley, Tanzania) but detected between distant populations (Cameroon vs. Tanzania) where differentiation was largely restricted to certain autosomal chromosomal inversions such as 2Rb. Overall, linkage disequilibrium within An. arabiensis decayed very rapidly (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium was observed within some inversions, suggesting that recombination is reduced in those regions. The overall low levels of linkage disequilibrium suggests that association studies in this taxon will be very challenging for all but variants of large effect, and will require large sample sizes.
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影响因子：
9.8
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Boyko AR;Quignon P;Li L;Schoenebeck JJ;Degenhardt JD;Lohmueller KE;Zhao K;Brisbin A;Parker HG;vonHoldt BM;Cargill M;Auton A;Reynolds A;Elkahloun AG;Castelhano M;Mosher DS;Sutter NB;Johnson GS;Novembre J;Hubisz MJ;Siepel A;Wayne RK;Bustamante CD;Ostrander EA
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