A genome-wide survey of structural variation between human and chimpanzee
A genome-wide survey of structural variation between human and chimpanzee
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DOI：
10.1101/gr.4338005
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发表时间：
2005-10-01
期刊：
影响因子：
7
通讯作者：
Eichler, EE
中科院分区：
文献类型：
--
作者：
Newman, TL;Tuzun, E;Eichler, EE
人类和黑猩猩基因组之间的结构变化（缺失、插入和倒置）可能对谱系特异性进化产生重大影响，因为它们可能发生戏剧性和不可逆转的突变。目前黑猩猩基因组组装的低质量性质妨碍了对许多这些差异的可靠鉴定。为了解决这一问题，我们采用了一种方法，将黑猩猩的fosmid配对端序列与人类基因组进行最优比对，系统地确定了两个物种之间>= 12 kb的结构变异位点。我们的分析共产生了651个推测的黑猩猩缺失位点（n = 293）、插入位点（n = 184），以及与两个基因组之间局部倒置一致的重排位点（n = 174）。我们使用PCR和Southern blot检测验证了一个子集（19/23）的插入和缺失，证实了我们方法的准确性。这些事件分布在整个基因组的所有染色体上，但与人类和黑猩猩的片段重复位点高度相关。这些结构变异包含至少24mb的DNA，并与bb10245个基因重叠。这些基因中有17个包含黑猩猩基因组序列中缺失的外显子，并且在黑猩猩中也显示出基因表达的显著减少。与尤尼斯、普拉卡什、杜特里罗和勒琼的开创性工作相比，这一分析将黑猩猩和人类之间潜在的重排数量扩大了50倍。此外，这项工作确定了黑猩猩基因组中有待进一步完成的区域的优先顺序，并为探究人类和黑猩猩之间的功能差异提供了资源。
Structural changes (deletions, insertions, and inversions) between human and chimpanzee genomes have likely had a significant impact on lineage-specific evolution because of their potential for dramatic and irreversible mutation. The low-quality nature of the Current chimpanzee genome assembly precludes the reliable identification of many of these differences. To circumvent this, we applied a method to optimally map chimpanzee fosmid paired-end sequences against the human genome to systematically identify sites of structural variation >= 12 kb between the two species. Our analysis yielded a total of 651 putative sites of chimpanzee deletion (n = 293), insertions (n = 184), and rearrangements consistent with local inversions between the two genomes (n = 174). We validated a Subset (19/23) of insertion and deletions using PCR and Southern blot assays, confirming the accuracy of our method. The events are distributed throughout the genome on all chromosomes but are highly correlated with sites of segmental duplication in human and chimpanzee. These structural variants encompass at least 24 Mb of DNA and overlap with >245 genes. Seventeen of these genes contain exons missing in the chimpanzee genomic sequence and also show a significant reduction in gene expression in chimpanzee. Compared with the pioneering work of Yunis, Prakash, Dutrillaux, and Lejeune, this analysis expands the number of potential rearrangements between chimpanzees and humans 50-fold. Furthermore, this work prioritizes regions for further finishing in the chimpanzee genome and provides a resource for interrogating functional differences between humans and chimpanzees.