High-throughput SNP genotyping: combining tag SNPs and molecular beacons.
High-throughput SNP genotyping: combining tag SNPs and molecular beacons.
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DOI：
10.1007/978-1-60327-411-1_17
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Mhlanga MM
中科院分区：
文献类型：
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作者：
Barreiro LB;Henriques R;Mhlanga MM
在过去的十年中，分子信标已成为单核苷酸多态性 (SNP) 多重分型中广泛使用的工具。标记这些探针的仪器和化学检测技术的改进使得每个反应孔可以使用多达六个光谱可区分的探针。随着人类基因组多样性表征方面取得的显着进展，描述不同人群基因组中 SNP 和单倍型变异的经验模式已成为可能。这些模式揭示了人类基因组的结构是由强连锁不平衡（LD）块组成的。由于 SNP 往往彼此处于 LD 状态，因此常见的单倍型共享共同的 SNP，因此一个区域中的大部分多样性可以通过对极少量的 SNP 进行分型来表征；所谓的标签 SNP。这就是分子信标多重能力的优势，因为可以使用少至 30 个探针以高通量方法询问多种单倍型。因此，通过结合使用标签SNP和分子信标，可以以高通量方式对个体进行临床相关单倍型分型，其成本比高通量测序方法低几个数量级。
In the last decade, molecular beacons have emerged to become a widely used tool in the multiplex typing of single nucleotide polymorphisms (SNPs). Improvements in detection technologies in instrumentation and chemistries to label these probes have made it possible to use up to six spectrally distinguishable probes per reaction well. With the remarkable advances made in the characterization of human genome diversity, it has been possible to describe empirical patterns of SNPs and haplotype variation in the genome of diverse human populations. These patterns have revealed that the human genome is structured in blocks of strong linkage disequilibrium (LD). Because SNPs tend to be in LD with each other, common haplotypes share common SNPs and thus the majority of the diversity in a region can be characterized by typing a very small number of SNPs; so-called tag SNPs. Herein lies the advantage of the multiplexing ability of molecular beacons, since it becomes possible to use as few as 30 probes to interrogate several haplotypes in a high-throughput approach. Thus, through the combined use of tag SNPs and molecular beacons it becomes possible to type individuals for clinically relevant haplotypes in a high-throughput manner at a cost that is orders of magnitude less than that for high throughput sequencing methods.