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

Xin Jin, Mingze He, Betsy Ferguson, Yuhuan Meng, Limei Ouyang, Jingjing Ren, Thomas Mailund, Fei Sun, Liangdan Sun, Juan Shen, Min Zhuo, Li Song, Jufang Wang, Fei Ling, Yuqi Zhu, Christina Hvilsom, Hans Siegismund, Xiaoming Liu, Zhuolin Gong, Fang Ji, Xinzhong Wang, Boqing Liu, Yu Zhang, Jianguo Hou, Jing Wang, Hua Zhao, Yanyi Wang, Xiaodong Fang, Guojie Zhang, Jian Wang, Xuejun Zhang, Mikkel H. Schierup, Hongli Du, Jun Wang, Xiaoning Wang

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.