Syvänen Ann-Christine
Department of Medical Sciences, Molecular Medicine, Uppsala University, Entr. 70, University Hospital, 75185 Uppsala, Sweden.
Nat Genet. 2005 Jun;37 Suppl:S5-10. doi: 10.1038/ng1558.
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.
全基因组关联研究使用单核苷酸多态性（SNP）标记有望识别复杂疾病背后的基因。全面的全基因组关联研究将需要数十万的SNP标记。尽管近期在高密度微阵列生产技术方面取得了许多进展，但开发基于微阵列的大规模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，这一步骤对于在大型二倍体基因组中降低SNP基因分型的复杂性并获得足够的灵敏度是必需的。PCR能够实现的多重水平与当前基于微阵列的方法不匹配，使得PCR成为检测中的限制步骤。最近通过巧妙地结合用于DNA扩增和SNP基因分型的知名反应原理，开发出了用于SNP基因分型的高度多重微阵列系统。只要与最佳SNP标记的选择、样本通量和检测成本相关的问题能够得到解决，这些新方法在可预见的未来就有对涉及复杂疾病的基因进行全基因组SNP定位的潜力。
