Nature：人类基因组内的结构变异研究新进展

生物谷

生物谷报道：关于人类遗传变异的大多数研究都集中在特定基因中单链核苷的差异上。但在更高的一个层次上，还存在结构差异，如插入、删除和倒转等，大小一般在几千个碱基对到数百个碱基对之间，这为遗传变异增添了另一个维度。在“国家人类基因组研究所”（NHGRI）主持下的一个新的研究项目，旨在积累一个关于人类基因组内结构变异的参照数据集，这个数据集能够为我们描绘出关于在表现型上正常的个体中所存在的DNA序列层次上的差异的一个全景图。该数据集也将成为在个别基因组层次上进行疾病研究的一条捷径。在本期Nature上，该项目的NHGRI工作组的成员详细介绍了这个项目的目的和方法。

FIGURE 1. Paired-end sequence approach.

Genomic libraries are constructed from fragmented DNA and subcloned into circular vectors such as BACs or fosmids. The ends of these fragment inserts are directly sequenced from universal vector primers near the subcloning site (arrows) and are termed end-sequence pairs or paired-end sequences. End-sequence pairs are mapped to their best location in the human reference genome sequence assembly. End-sequence pairs that are discordant in terms of length (> 3 s.d. from the mean insert length) and/or orientation when mapped against the reference genome assembly may be indicative of deletions, insertions or inversion, as indicated (red, blue and green, respectively). End-sequence pairs consistent in terms of length and orientation are shown as grey.

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