Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies
Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies
复制标题
DOI：
10.1093/hmg/ddn002
复制
发表时间：
2008-04-15
影响因子：
3.5
通讯作者：
Lee, Charles
中科院分区：
文献类型：
--
作者：
Lee, Arthur S.;Gutierrez-Arcelus, Maria;Lee, Charles
拷贝数变异（CNVs）是正常个体基因组DNA的遗传增益和损失。虽然拷贝数变异在人类中得到了广泛的研究，但我们对其他哺乳动物物种的拷贝数变异的了解更为有限。基于恒河猴（Macaca mulatta）的参考基因组序列，我们设计了一个定制的基于阵列的比较基因组杂交（aCGH）平台。恒河猴是生物医学研究中研究最广泛的非人类灵长类动物。我们使用该平台在10个无亲缘关系的猕猴个体中鉴定了123个CNVs，其中24%的CNVs在多个个体中观察到。我们发现，在猕猴CNV位点上，片段重复显著富集。我们还观察到恒河猴和人类CNV之间存在显著的重叠，这表明某些基因组区域容易发生反复的CNV形成和不稳定性，甚至在灵长类动物进化的5000万年（类似于每个谱系的2500万年）中也是如此。此外，对于在人类和猕猴中观察到的8种CNVs，先前的人类研究报告了拷贝数与基因表达或疾病易感性之间的关系。因此，恒河猴提供了一个有趣的，非人类灵长类动物的近亲繁殖的模式生物，与表型相关的人类CNVs的特定功能的假设可以被测试。
Copy number variants (CNVs) are heritable gains and losses of genomic DNA in normal individuals. While copy number variation is widely studied in humans, our knowledge of CNVs in other mammalian species is more limited. We have designed a custom array-based comparative genomic hybridization (aCGH) platform with 385 000 oligonucleotide probes based on the reference genome sequence of the rhesus macaque (Macaca mulatta), the most widely studied non-human primate in biomedical research. We used this platform to identify 123 CNVs among 10 unrelated macaque individuals, with 24% of the CNVs observed in multiple individuals. We found that segmental duplications were significantly enriched at macaque CNV loci. We also observed significant overlap between rhesus macaque and human CNVs, suggesting that certain genomic regions are prone to recurrent CNV formation and instability, even across a total of similar to 50 million years of primate evolution (similar to 25 million years in each lineage). Furthermore, for eight of the CNVs that were observed in both humans and macaques, previous human studies have reported a relationship between copy number and gene expression or disease susceptibility. Therefore, the rhesus macaque offers an intriguing, non-human primate outbred model organism with which hypotheses concerning the specific functions of phenotypically relevant human CNVs can be tested.