Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization
Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization
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DOI：
10.1007/s00439-005-0130-9
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发表时间：
2006-03-01
期刊：
影响因子：
5.3
通讯作者：
Kehrer-Sawatzki, H
中科院分区：
文献类型：
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作者：
Goidts, V;Armengol, L;Kehrer-Sawatzki, H
拷贝数差异（CNDs）及其伴随的基因数差异是人类和其他灵长类动物基因组差异的重要原因。为了评估其相对重要性，利用高分辨率人类BAC阵列（aCGH）对人类、普通黑猩猩、倭黑猩猩、大猩猩、猩猩和猕猴的基因组进行了比较。为了避免频繁的种内多态性的潜在干扰，我们使用了来自每个物种的汇总DNA样本。共鉴定出322个大型种间CND位点。大多数CNDs是谱系特异性的，但谱系之间的频率差异很大；类人猿中CND频率最高的是大猩猩。猩猩基因组的保守性已经被核型研究注意到，我们的研究结果表明，这种程度的保护可能延伸到亚微观水平。在确定的322个CND位点中，观察到14个人类谱系特异性增益。大多数这些人类特异性拷贝数的增加跨越了以前被确定为片段复制（SDs）的区域，我们的研究表明，SDs是人类和其他灵长类动物基因组之间CND的主要位点。aCGH检测到的人类特异性CNDs中有4个位于人类特异性核型变化的断点附近[例如，人类特异性1号染色体反转和多态反转inv(2)(p11.2q13)]，这表明人类特异性重复可能易导致染色体重排。人类特异性拷贝数增加与染色体断点的关联强调了它们在介导核型进化以及促进人类基因组多样性方面的潜在重要性。
Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.