Highly multiplexed molecular inversion probe genotyping: Over 10,000 targeted SNPs genotyped in a single tube assay
Highly multiplexed molecular inversion probe genotyping: Over 10,000 targeted SNPs genotyped in a single tube assay
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DOI：
10.1101/gr.3185605
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发表时间：
2005-02-01
期刊：
影响因子：
7
通讯作者：
Gibbs, RA
中科院分区：
文献类型：
--
作者：
Hardenbol, P;Yu, FL;Gibbs, RA
大规模的遗传学研究高度依赖于高效和可扩展的多重SNP分析。在这项研究中，我们报道了四色、单阵列检测的分子反转探针技术的发展，应用于Lip的大规模基因分型，每个反应有12,000个SNPs。作为国际HapMap项目的一部分，我们使用这项技术在人类中心家庭小组的30个三联体中产生了38,429个SNP分析，我们建立了类似于90%的SNP转换率，符合率为99.6%，完整性水平>；98%，多重分析高达12,000个水平。此外，这些单独的指标可以“权衡”，通过牺牲一小部分转换率，准确度可以提高到非常高的水平。当从6,000多路扩展到12,000多路检测时，没有发现性能损失，这有力地验证了该技术在高多路水平下抑制交叉反应的能力。这项研究的结果表明，这项技术适用于在间接连锁不平衡研究中使用靶向SNPs的综合关联研究，或直接筛查致病突变。
Large-scale genetic Studies are highly dependent on efficient and scalable multiplex SNP assays. In this study, we report the development of Molecular Inversion Probe technology with four-color, single array detection, applied to large-scale genotyping Of Lip to 12,000 SNPs per reaction. While generating 38,429 SNP assays using this technology in a population of 30 trios from the Centre d'Etude Polymorphisme Humain family panel as part of the International HapMap project, we established SNP conversion rates of similar to90% with concordance rates >99.6% and completeness levels >98% for assays multiplexed up to 12,000plex levels. Furthermore, these individual metrics can be "traded off" and, by sacrificing a small fraction of the conversion rate, the accuracy can be increased to very high levels. No loss of performance is seen when scaling from 6,000plex to 12,000plex assays, strongly validating the ability of the technology to Suppress cross-reactivity at high multiplex levels. The results Of this Study demonstrate the Suitability of this technology for comprehensive association studies that use targeted SNPs in indirect linkage disequilibrium Studies or that directly screen for causative mutations.