Toward genome-wide SNP genotyping
Toward genome-wide SNP genotyping
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DOI：
10.1038/ng1558
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发表时间：
2005-06-01
期刊：
影响因子：
30.8
通讯作者：
Syvänen, AC
中科院分区：
文献类型：
--
作者：
Syvänen, AC
与SNP标记的全基因组关联研究有望使复杂疾病的基因鉴定成为可能。全面的全基因组关联研究将需要数十万个SNP标记。尽管高密度微阵列的生产技术最近取得了许多进展，但在这种规模上开发基于微阵列的SNP基因分型方法仍然是一项艰巨的任务。一个关键的技术障碍是PCR扩增步骤，这需要降低复杂性并获得足够的灵敏度来对大型二倍体基因组中的snp进行基因分型。PCR可实现的多路复用水平与当前基于微阵列的方法不匹配，使PCR成为检测中的限制性步骤。高度复用的SNP基因分型微阵列系统最近以巧妙的方式结合了众所周知的DNA扩增反应原理和SNP基因分型。这些新方法提供了在可预见的未来对涉及复杂疾病的基因进行全基因组SNP定位的潜力，前提是可以解决与最佳SNP标记的选择、样品吞吐量和检测成本相关的问题。
Genome-wide association studies with SNP markers are expected to allow identification of genes that underlie complex disorders. Hundreds of thousands of SNP markers will be required for comprehensive genome-wide association studies. The development of microarray-based methods for SNP genotyping on this scale remains a demanding task, despite many recent advances in technology for the production of high-density microarrays. A key technical obstacle is the PCR amplification step, which is required to reduce the complexity of and gain sufficient sensitivity for genotyping SNPs in large, diploid genomes. The multiplexing level that can be achieved in PCR does not match that of current microarray-based methods, making PCR the limiting step in the assays. Highly multiplexed microarray systems for SNP genotyping have recently been developed by combining well-known reaction principles for DNA amplification and SNP genotyping in clever ways. These new methods offer the potential of genome-wide SNP mapping of genes involved in complex diseases in the foreseeable future, provided that issues related to selection of the optimal SNP markers, sample throughput and the cost of the assays can be addressed.