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Tracing two causative SNPs reveals SARS-CoV-2 transmission in North America population

By Xumin Ou, Zhishuang Yang, Dekang Zhu, Sai Mao, Mingshu Wang, Renyong Jia, Shun Chen, Mafeng Liu, Qiao Yang, Ying Wu, Xinxin Zhao, Shaqiu Zhang, Juan huang, Qun Gao, Yunya Liu, Ling Zhang, Maikel Peopplenbosch, Qiuwei Pan, Anchun Cheng

Posted 14 May 2020
bioRxiv DOI: 10.1101/2020.05.12.092056

During the COVID-19 pandemic, precisely tracing the route of the SARS-CoV-2 transmission in human population remains challenging. Because this RNA virus can mutate rapidly without a specifically tracing maker. Herein, using a geographic stratified genome-wide association study (GWAS) of 2599 full-genome sequences, we identified that two SNPs (i.e., 1059.C>T and 25563.G>T) of linkage disequilibrium were presented in approximately half of North America SARS-CoV-2 population (p=2.44 x10-212 and p=2.98 x 10-261), resulting two missense mutations (i.e., Thr 265 Ile and Gln 57 His) in ORF1ab and ORF3a, respectively. Interestingly, these two SNPs exclusively occurred in the North America dominated clade 1, accumulated during mid to late March, 2020. We did not find any of these two SNPs by retrospectively tracing the two SNPs in bat and pangolin related SARS-CoV-2 and human SARS-CoV-2 from the first epicenter Wuhan or other regions of China mainland. This suggests that the SARS-CoV-2 population of Chinese mainland were different from the prevalent strains of North America. Time-dependently, we found that these two SNPs first occurred in Europe SARS-CoV-2 (26-Feb-2020) which was 3 days early than the occurring date of North America isolates and 17 days early for Asia isolates (Taiwan district of China dominated). Collectively, this population genetic analysis highlights a well-confidential transmission route of the North America isolates and the two SNPs we newly identified are possibly novel diagnosable or druggable targets for surveillance and treatment. ### Competing Interest Statement The authors have declared no competing interest.

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