Lipshutz R J, Morris D, Chee M, Hubbell E, Kozal M J, Shah N, Shen N, Yang R, Fodor S P
Affymetrix, Santa Clara, CA, USA.
Biotechniques. 1995 Sep;19(3):442-7.
As the Human Genome Project and related efforts identify and determine the DNA sequences of human genes, it is important that highly reliable and efficient mechanisms are found to access individual genetic variation. It is only through a greater understanding of genetic diversity that the true benefit of the Human Genome Project will be realized. One approach, hybridization to high-density arrays of oligonucleotides, is a fast and effective means of accessing this genetic variation. Light-directed chemical synthesis has been used to generate miniaturized, high-density arrays of oligonucleotide probes. Application-specific oligonucleotide probe array designs have been developed for the rapid screening of characterized genes. Dedicated instrumentation and software have been developed for array hybridization, fluorescence detection and data acquisition and analysis. In a specific and challenging application, oligonucleotide probe arrays have been used to screen the reverse transcriptase and protease genes of the highly polymorphic HIV-1 genome to explore genetic diversity and detect mutations conferring resistance to antiviral drugs. Results from this application strongly suggest that oligonucleotide probe arrays will be a powerful tool for rapid investigations in sequence checking, pathogen detection, expression monitoring and DNA molecular recognition.
随着人类基因组计划及相关工作确定人类基因的DNA序列，找到高度可靠且高效的机制来获取个体遗传变异至关重要。只有通过更深入地了解遗传多样性，人类基因组计划的真正益处才能得以实现。一种方法是与高密度寡核苷酸阵列杂交，这是获取这种遗传变异的快速有效手段。光导向化学合成已用于生成小型化、高密度的寡核苷酸探针阵列。已开发出针对特定应用的寡核苷酸探针阵列设计，用于快速筛选已表征的基因。已开发出专门的仪器和软件用于阵列杂交、荧光检测以及数据采集和分析。在一个特定且具有挑战性的应用中，寡核苷酸探针阵列已用于筛选高度多态的HIV-1基因组的逆转录酶和蛋白酶基因，以探索遗传多样性并检测赋予抗病毒药物抗性的突变。该应用的结果有力地表明，寡核苷酸探针阵列将成为序列检查、病原体检测、表达监测和DNA分子识别快速研究的强大工具。
