The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase. In another embodiment, the end labeling can be accomplished by providing a nucleic acid, providing labeled nucleoside triphosphates, and attaching the nucleoside triphosphates to the nucleic acid using a terminal transferase.
本发明提供了一种用于鉴定两个或多个样本之间核酸丰度(如表达
水平)差异的简化方法。该方法包括提供一个包含大量(如超过 1000 个)任意选择的不同寡核苷酸探针的阵列,其中每个不同探针的序列和位置都是已知的。来自两个或多个样本的核酸样本(如 mRNA)与探针阵列杂交,并检测杂交模式。样本间杂交模式的差异表明这些样本间各种
基因表达的差异。本发明还提供了一种对核酸进行末端标记的方法。在一个实施方案中,该方法包括提供核酸,提供标记的寡核苷酸,然后将寡核苷酸酶联到核酸上。因此,例如,当核酸是 RNA 时,可使用 RNA 连接酶将标记的寡核苷酸连接到核酸上。在另一个实施方案中,末端标记可以通过提供核酸、提供标记的核苷
三磷酸酯以及使用末端转移酶将核苷
三磷酸酯连接到核酸上来完成。