Building the sequence map of the human pan-genome

Ruiqiang Li, Yingrui Li, Hancheng Zheng, Ruibang Luo, Hongmei Zhu, Qibin Li, Wubin Qian, Yuanyuan Ren, Geng Tian, Jinxiang Li, Guangyu Zhou, Xuan Zhu, Honglong Wu, Junjie Qin, Xin Jin, Dongfang Li, Hongzhi Cao, Xueda Hu, Hélène Blanche, Howard Cann, Xiuqing Zhang, Songgang Li, Lars Bolund, Karsten Kristiansen, Huanming Yang, Jun Wang, Jian Wang

Here we integrate the de novo assembly of an Asian and an African genome with the NCBI reference human genome, as a step toward constructing the human pan-genome. We identified approximately 5 Mb of novel sequences not present in the reference genome in each of these assemblies. Most novel sequences are individual or population specific, as revealed by their comparison to all available human DNA sequence and by PCR validation using the human genome diversity cell line panel. We found novel sequences present in patterns consistent with known human migration paths. Cross-species conservation analysis of predicted genes indicated that the novel sequences contain potentially functional coding regions. We estimate that a complete human pan-genome would contain approximately 19-40 Mb of novel sequence not present in the extant reference genome. The extensive amount of novel sequence contributing to the genetic variation of the pan-genome indicates the importance of using complete genome sequencing and de novo assembly.