An Effort to Use Human-Based Exome Capture Methods to Analyze Chimpanzee and Macaque Exomes

作者:Jin, Xin*; He, Mingze; Ferguson, Betsy; Meng, Yuhuan; Ouyang, Limei; Ren, Jingjing; Mailund, Thomas; Sun, Fei; Sun, Liangdan; Shen, Juan; Zhuo, Min; Song, Li; Wang, Jufang; Ling, Fei; Zhu, Yuqi; Hvilsom, Christina; Siegismund, Hans; Liu, Xiaoming; Gong, Zhuolin; Ji, Fang; Wang, Xinzhong; Liu, Boqing; Zhang, Yu; Hou, Jianguo; Wang, Jing; Zhao, Hua; Wang, Yanyi; Fang, Xiaodong; Zhang, Guojie; Wang, Jian; Zhang, Xuejun; Schierup, Mikkel H.; Du, Hongli; Wang, Jun; Wang, Xiaoning
来源:PLos One, 2012, 7(7): e40637.
DOI:10.1371/journal.pone.0040637

摘要

Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%-77.3%) of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.