Efficient identification of rare variants in large populations: deep re-sequencing the CRP locus in the CARDIA study.
Efficient identification of rare variants in large populations: deep re-sequencing the CRP locus in the CARDIA study.
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DOI：
10.1093/nar/gkt092
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发表时间：
2013-04
影响因子：
14.9
通讯作者：
Carlson CS
中科院分区：
文献类型：
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作者：
Chen CT;McDavid AN;Kahsai OJ;Zebari AS;Carlson CS
在全基因组关联研究中发现的许多常见单核苷酸多态性的效应大小通常只能解释各种性状中估计的总遗传力的一小部分。一种假设是，影响较大的罕见变异可能是遗传缺失的原因。尽管测序技术取得了进步，但在大量人群中发现罕见变异在经济上仍然具有挑战性。对汇集的样本进行测序可以降低成本，但检测罕见变异和识别单个携带者是困难的，需要额外的实验。为了解决这些问题，我们开发了一种罕见变异检测算法V-Sieve来筛选混合DNA样本中的罕见等位基因，该算法与独特的池化策略相结合，能够有效地筛选数千个样本中的特异性变异候选基因。我们将该方法应用于2283个个体，在c反应蛋白位点发现了bbbb100个多态性，等位基因频率低至0.02%，阳性预测率为93%。我们相信该算法在筛选已知与特定表型相关的基因组区域的罕见变异以及复制在大规模研究中发现的罕见变异关联（如外显子组重测序项目）方面都是有用的。
Effect sizes of many common single nucleotide polymorphisms identified in genome-wide association studies generally explain only a modest fraction of the total estimated heritability in a variety of traits. One hypothesis is that rare variants with larger effects might account for the missing heritability. Despite advances in sequencing technology, discovering rare variants in a large population is still economically challenging. Sequencing pooled samples can reduce the cost, but detecting rare variants and identifying individual carriers is difficult and requires additional experiments. To address these issues, we have developed a rare variant-detection algorithm V-Sieve to screen for rare alleles in pooled DNA samples which, in combination with a unique pooling strategy, is able to efficiently screen a candidate gene for idiosyncratic variants in thousands of samples. We applied this method to 2283 individuals, and identified >100 polymorphisms in the C-reactive protein locus at an allele frequency as low as 0.02%, with a positive predictive rate of 93%. We believe this algorithm will be useful in both screening for rare variants in genomic regions known to associate with particular phenotypes and in replicating rare variant associations identified in large-scale studies, such as exome re-sequencing projects.
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影响因子：
5.3
作者：
Peters U;Hutter CM;Hsu L;Schumacher FR;Conti DV;Carlson CS;Edlund CK;Haile RW;Gallinger S;Zanke BW;Lemire M;Rangrej J;Vijayaraghavan R;Chan AT;Hazra A;Hunter DJ;Ma J;Fuchs CS;Giovannucci EL;Kraft P;Liu Y;Chen L;Jiao S;Makar KW;Taverna D;Gruber SB;Rennert G;Moreno V;Ulrich CM;Woods MO;Green RC;Parfrey PS;Prentice RL;Kooperberg C;Jackson RD;Lacroix AZ;Caan BJ;Hayes RB;Berndt SI;Chanock SJ;Schoen RE;Chang-Claude J;Hoffmeister M;Brenner H;Frank B;Bézieau S;Küry S;Slattery ML;Hopper JL;Jenkins MA;Le Marchand L;Lindor NM;Newcomb PA;Seminara D;Hudson TJ;Duggan DJ;Potter JD;Casey G
通讯作者：
Casey G
多阶段全基因组关联研究确定了七个前列腺癌易感位点
影响因子：
30.8
作者：
通讯作者：
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
3.5
作者：
Chen, Christina T. L.;Fernandez-Rhodes, Lindsay;Franceschini, Nora
通讯作者：
Franceschini, Nora
影响因子：
30.8
作者：
通讯作者：
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