Association mapping of insecticide resistance in wild Anopheles gambiae populations: major variants identified in a low-linkage disequilbrium genome.
Association mapping of insecticide resistance in wild Anopheles gambiae populations: major variants identified in a low-linkage disequilbrium genome.
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DOI：
10.1371/journal.pone.0013140
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发表时间：
2010-10-01
期刊：
影响因子：
3.7
通讯作者：
Donnelly MJ
中科院分区：
文献类型：
--
作者：
Weetman D;Wilding CS;Steen K;Morgan JC;Simard F;Donnelly MJ
关联研究是揭示野生种群复杂性状遗传基础的一种很有前途的方法。预测研究的成功需要关于群体分层、连锁不平衡和不同性状类型的变异效应大小分布的数据，但大多数类群缺乏这些数据。我们量化和调查这些关键变量的影响，在一个大规模的关联研究的一个强有力的选择性状的医学重要性：拟除虫菊酯的耐药性在非洲疟疾媒介冈比亚按蚊。我们使用富含候选杀虫剂抗性基因SNP的1536-SNP阵列对来自加纳和喀麦隆的1500只抗性表型野生蚊子进行基因分型。三个因素对学习力有很大影响。(1)群体分层，这是由于共同出现的分子形式（M和S），和神秘的内部形式分层需要分区分析和基因组控制。(2)所有显著影响的SNP（优势比，OR>2）都是罕见的（次要等位基因频率，MAF<0.05）。(3)在大部分基因组中，连锁不平衡（LD）非常低。然而，与最近的选择性扫描一致的局部高LD，以及每个子样本中一致的高OR，有助于直接和间接检测已知杀虫剂靶位点突变kdr L1014 F（OR ≥ 6; P<10−6），但耐药水平受局部单倍型背景影响。由于野生A.冈比亚，LD为基础的关联映射是具有挑战性的，但至少是可行的主要影响变量，特别是在LD是通过选择性扫描增强。这些变体对于预测性诊断筛选将是最重要的。
Association studies are a promising way to uncover the genetic basis of complex traits in wild populations. Data on population stratification, linkage disequilibrium and distribution of variant effect-sizes for different trait-types are required to predict study success but are lacking for most taxa. We quantified and investigated the impacts of these key variables in a large-scale association study of a strongly selected trait of medical importance: pyrethroid resistance in the African malaria vector Anopheles gambiae. We genotyped ≈1500 resistance-phenotyped wild mosquitoes from Ghana and Cameroon using a 1536-SNP array enriched for candidate insecticide resistance gene SNPs. Three factors greatly impacted study power. (1) Population stratification, which was attributable to co-occurrence of molecular forms (M and S), and cryptic within-form stratification necessitating both a partitioned analysis and genomic control. (2) All SNPs of substantial effect (odds ratio, OR>2) were rare (minor allele frequency, MAF<0.05). (3) Linkage disequilibrium (LD) was very low throughout most of the genome. Nevertheless, locally high LD, consistent with a recent selective sweep, and uniformly high ORs in each subsample facilitated significant direct and indirect detection of the known insecticide target site mutation kdr L1014F (OR≈6; P<10−6), but with resistance level modified by local haplotypic background. Primarily as a result of very low LD in wild A. Gambiae, LD-based association mapping is challenging, but is feasible at least for major effect variants, especially where LD is enhanced by selective sweeps. Such variants will be of greatest importance for predictive diagnostic screening.
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DOI：
10.1073/pnas.0906182107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Eyre-Walker, Adam
通讯作者：
Eyre-Walker, Adam
影响因子：
3
作者：
Czeher, Cyrille;Labbo, Rabiou;Duchemin, Jean-Bernard
通讯作者：
Duchemin, Jean-Bernard
影响因子：
4.4
作者：
Cohuet A;Krishnakumar S;Simard F;Morlais I;Koutsos A;Fontenille D;Mindrinos M;Kafatos FC
通讯作者：
Kafatos FC
影响因子：
30.8
作者：
Jallow, Muminatou;Teo, Yik Ying;Small, Kerrin S.;Rockett, Kirk A.;Deloukas, Panos;Clark, Taane G.;Kivinen, Katja;Bojang, Kalifa A.;Conway, David J.;Pinder, Margaret;Sirugo, Giorgio;Sisay-Joof, Fatou;Usen, Stanley;Auburn, Sarah;Bumpstead, Suzannah J.;Campino, Susana;Coffey, Alison;Dunham, Andrew;Fry, Andrew E.;Green, Angela;Gwilliam, Rhian;Hunt, Sarah E.;Inouye, Michael;Jeffreys, Anna E.;Mendy, Alieu;Palotie, Aarno;Potter, Simon;Ragoussis, Jiannis;Rogers, Jane;Rowlands, Kate;Somaskantharajah, Elilan;Whittaker, Pamela;Widden, Claire;Donnelly, Peter;Howie, Bryan;Marchini, Jonathan;Morris, Andrew;SanJoaquin, Miguel;Achidi, Eric Akum;Agbenyega, Tsiri;Allen, Angela;Amodu, Olukemi;Corran, Patrick;Djimde, Abdoulaye;Dolo, Amagana;Doumbo, Ogobara K.;Drakeley, Chris;Dunstan, Sarah;Evans, Jennifer;Farrar, Jeremy;Fernando, Deepika;Hien, Tran Tinh;Horstmann, Rolf D.;Ibrahim, Muntaser;Karunaweera, Nadira;Kokwaro, Gilbert;Koram, Kwadwo A.;Lemnge, Martha;Makani, Julie;Marsh, Kevin;Michon, Pascal;Modiano, David;Molyneux, Malcolm E.;Mueller, Ivo;Parker, Michael;Peshu, Norbert;Plowe, Christopher V.;Puijalon, Odile;Reeder, John;Reyburn, Hugh;Riley, Eleanor M.;Sakuntabhai, Anavaj;Singhasivanon, Pratap;Sirima, Sodiomon;Tall, Adama;Taylor, Terrie E.;Thera, Mahamadou;Troye-Blomberg, Marita;Williams, Thomas N.;Wilson, Michael;Kwiatkowski, Dominic P.
通讯作者：
Kwiatkowski, Dominic P.
DOI：
10.1016/j.trstmh.2009.01.008
发表时间：
2009-11-01
影响因子：
2.2
作者：
Dabire, K. R.;Diabate, A.;Baldet, T.
通讯作者：
Baldet, T.