The Genome-Wide Association Study-A New Era for Common Polygenic Disorders
The Genome-Wide Association Study-A New Era for Common Polygenic Disorders
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DOI：
10.1007/s12265-010-9178-6
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发表时间：
2010-06-01
影响因子：
3.4
通讯作者：
Chen, Li
中科院分区：
文献类型：
--
作者：
Roberts, Robert;Wells, George A.;Chen, Li
本文综述了近十年来利用高密度单核苷酸微阵列技术筛查人类基因组遗传风险变异的进展，并概述了未来深入研究人类遗传前沿的策略。人类基因组的序列提供了生命的蓝图，而其变异则提供了生命的调味品。大约99.5%的人类基因组DNA序列在人类中是相同的，其中0.5%的基因组序列（1500万bp）占所有个体差异，包括对疾病的易感性。计算机芯片阵列的新技术包含多达数百万个SNP作为DNA标记，使全基因组关联研究成为可能，以检测常见多基因疾病（如冠状动脉疾病）的遗传易感性。这些研究所需的样本量是巨大的，已经形成了世界范围的联盟，如CARDIoadministration，以适应这一要求。在过去的2年里，随着9p21的鉴定以及其他几个人的鉴定，进展是显着的。预计大多数常见变异（次要等位基因频率，MAF >5%）将在未来2至3年内被鉴定为CAD。罕见变体（MAF
This review covers the advances made in the last decade utilizing the high-density single-nucleotide microarrays to screen the entire human genome for genetic risk variants and outlines future strategies to draw deeper into the human genetic front. The sequence of the human genome provides the blueprint for life, while its variation provides the spice of life. Approximately 99.5% of the human genome DNA sequence is identical among humans with 0.5% of the genome sequence (15 million bps) accounting for all individual differences including susceptibility for disease. The new technology of the computerized chip array containing up to millions of SNPs as DNA markers makes possible genome-wide association studies to detect genetic predisposition to common polygenic disorders such as coronary artery disease (CAD). The sample sizes required for these studies are massive and large; worldwide consortiums such as CARDIoGRAM have been formed to accommodate this requirement. The progress has been remarkable with the identification of 9p21 followed by several others within the past 2 years. It is expected that most of the common variants (minor allele frequency, MAF >5%) will be identified for CAD within the next 2 to 3 years. Rare variants (MAF