Closing gaps in the human genome with fosmid resources generated from multiple individuals
Closing gaps in the human genome with fosmid resources generated from multiple individuals
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DOI：
10.1038/ng.2007.34
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发表时间：
2008-01-01
期刊：
影响因子：
30.8
通讯作者：
Kaul, Rajinder
中科院分区：
文献类型：
--
作者：
Bovee, Donald;Zhou, Yang;Kaul, Rajinder
人类基因组序列已经以很高的标准完成；然而，当国际人类基因组测序联盟在2004年公布完成的基因组时，仍有340多个缺口。利用从多个个体产生的fosmid资源，我们针对人类基因组常染色质部分的缺口。在此我们报道了2488842bp之前未知的常染色质序列，其中363114bp填补了250个常染色质缺口中的26个，即10%，包括19号染色体上剩余的两个常染色质缺口。发现8个（30.7%）被填补的缺口具有多态性。这些序列使得几个人类基因能够被完整注释以及mRNA能够被定位。与整个基因组相比，缺口序列中节段性重复序列的富集程度是其2.3倍。我们的分析证实，“完成的”基因组内并非所有缺口都难以进行亚克隆，并表明成对末端测序的fosmid文库可能被证明是完成人类常染色质基因组的丰富资源。
The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome.