Alu recombination-mediated structural deletions in the chimpanzee genome
Alu recombination-mediated structural deletions in the chimpanzee genome
复制标题
DOI：
10.1371/journal.pgen.0030184
复制
发表时间：
2007-10-01
期刊：
影响因子：
4.5
通讯作者：
Batzer, Mark A.
中科院分区：
文献类型：
--
作者：
Han, Kyudong;Lee, Jungnam;Batzer, Mark A.
Alu元件拥有超过120万个拷贝，是灵长类基因组结构变异的最重要来源之一。在这里，我们比较了黑猩猩和人类基因组，以确定黑猩猩基因组中Alu重组介导的缺失（ARMD）的程度，因为黑猩猩和人类谱系的分歧（类似于600万年前）。结合计算数据分析和实验验证，我们已经确定了663黑猩猩谱系特异性缺失（涉及总相似的771 kb的基因组序列）归因于这一过程。ARMD事件基本上抵消了由黑猩猩特异性Alu插入引起的基因组扩增。RefSeq数据库表明，在黑猩猩谱系中，6个基因中的13个外显子（注释为在人类基因组中可证实或可证实的功能性）和299个内含子区域已通过ARMD被删除。因此，我们的数据表明，这一过程可能有助于黑猩猩和人类之间的基因组和表型多样性。此外，我们发现四个独立的ARMD事件在orthopathic位点的大猩猩或猩猩基因组。这表明，在其他非人灵长类动物基因组中已经发生ARMD事件的基因座的人类直系同源物可能是未来缺失的“风险”基序，这可能随后导致人类谱系特异性遗传重排和疾病。
With more than 1.2 million copies, Alu elements are one of the most important sources of structural variation in primate genomes. Here, we compare the chimpanzee and human genomes to determine the extent of Alu recombination-mediated deletion (ARMD) in the chimpanzee genome since the divergence of the chimpanzee and human lineages (similar to 6 million y ago). Combining computational data analysis and experimental verification, we have identified 663 chimpanzee lineage-specific deletions (involving a total of similar to 771 kb of genomic sequence) attributable to this process. The ARMD events essentially counteract the genomic expansion caused by chimpanzee-specific Alu inserts. The RefSeq databases indicate that 13 exons in six genes, annotated as either demonstrably or putatively functional in the human genome, and 299 intronic regions have been deleted through ARMDs in the chimpanzee lineage. Therefore, our data suggest that this process may contribute to the genomic and phenotypic diversity between chimpanzees and humans. In addition, we found four independent ARMD events at orthologous loci in the gorilla or orangutan genomes. This suggests that human orthologs of loci at which ARMD events have already occurred in other nonhuman primate genomes may be ``at-risk'' motifs for future deletions, which may subsequently contribute to human lineage-specific genetic rearrangements and disorders.