Zhuo D, Zhao W D, Wright F A, Yang H Y, Wang J P, Sears R, Baer T, Kwon D H, Gordon D, Gibbs S, Dai D, Yang Q, Spitzner J, Krahe R, Stredney D, Stutz A, Yuan B
Bioinformatics Group, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA.
Genome Res. 2001 May;11(5):904-18. doi: 10.1101/gr.gr-1645r.
The recent release of the first draft of the human genome provides an unprecedented opportunity to integrate human genes and their functions in a complete positional context. However, at least three significant technical hurdles remain: first, to assemble a complete and nonredundant human transcript index; second, to accurately place the individual transcript indices on the human genome; and third, to functionally annotate all human genes. Here, we report the extension of the UNIGENE database through the assembly of its sequence clusters into nonredundant sequence contigs. Each resulting consensus was aligned to the human genome draft. A unique location for each transcript within the human genome was determined by the integration of the restriction fingerprint, assembled genomic contig, and radiation hybrid (RH) maps. A total of 59,500 UNIGENE clusters were mapped on the basis of at least three independent criteria as compared with the 30,000 human genes/ESTs currently mapped in Genemap'99. Finally, the extension of the human transcript consensus in this study enabled a greater number of putative functional assignments than the 11,000 annotated entries in UNIGENE. This study reports a draft physical map with annotations for a majority of the human transcripts, called the Human Index of Nonredundant Transcripts (HINT). Such information can be immediately applied to the discovery of new genes and the identification of candidate genes for positional cloning.
人类基因组初稿的近期发布为在完整的位置背景下整合人类基因及其功能提供了前所未有的机遇。然而，至少仍存在三个重大技术障碍：其一，构建一个完整且无冗余的人类转录本索引；其二，将各个转录本索引准确置于人类基因组上；其三，对所有人类基因进行功能注释。在此，我们报告了通过将其序列簇组装成无冗余序列重叠群来扩展UNIGENE数据库。将每个得到的共有序列与人类基因组草图进行比对。通过整合限制性指纹图谱、组装的基因组重叠群和辐射杂种（RH）图谱，确定了人类基因组内每个转录本的唯一位置。与目前在Genemap'99中定位的30,000个人类基因/EST相比，基于至少三个独立标准共定位了59,500个UNIGENE簇。最后，本研究中人类转录本共有序列的扩展使得能够进行比UNIGENE中11,000个注释条目更多的假定功能分配。本研究报告了一个带有大多数人类转录本注释的物理图谱草图，称为非冗余转录本人类索引（HINT）。此类信息可立即应用于新基因的发现以及定位克隆候选基因的鉴定。
