Genomic surveillance of Nevada patients revealed prevalence of unique SARS-CoV-2 variants bearing mutations in the RdRp gene

Paul D. Hartley; Richard L. Tillett; David P. AuCoin; Joel R. Sevinsky; Yanji Xu; Andrew Gorzalski; Mark Pandori; Erin Buttery; Holly Hansen; Michael A. Picker; Cyprian C. Rossetto; Subhash C. Verma

doi:10.1016/j.jgg.2021.01.004

Volume 48 Issue 1

Jan. 2021

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Article Navigation > Journal of Genetics and Genomics > 2021 > 48(1): 40-51

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Genomic surveillance of Nevada patients revealed prevalence of unique SARS-CoV-2 variants bearing mutations in the RdRp gene

doi: 10.1016/j.jgg.2021.01.004

a
Nevada Genomics Center, Reno, NV 89557, USA
b
University of Nevada, Reno, Reno, NV 89557, USA
c
Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USA
d
Department of Microbiology & Immunology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA
e
Theiagen Consulting, LLC, Highlands Ranch, CO 80128, USA
f
Nevada Center for Bioinformatics, Reno, NV 89557, USA
g
Nevada State Public Health Laboratory, Reno, NV 89503, USA
h
Southern Nevada Public Health Laboratory of the Southern Nevada Health District, Las Vegas, NV 89107, USA

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Corresponding author: E-mail address: crossetto@med.unr.edu (Cyprian C. Rossetto); E-mail address: scverma@med.unr.edu (Subhash C. Verma)
Publish Date: 2021-01-20

Abstract

Abstract

Patients with signs of COVID-19 were tested through diagnostic RT-PCR for SARS-CoV-2 using RNA extracted from the nasopharyngeal/nasal swabs. To determine the variants of SARS-CoV-2 circulating in the state of Nevada, specimens from 200 COVID-19 patients were sequenced through our robust sequencing platform, which enabled sequencing of SARS-CoV-2 from specimens with even very low viral loads, without the need of culture-based amplification. High genome coverage allowed the identification of single and multi-nucleotide variants in SARS-CoV-2 in the community and their phylogenetic relationships with other variants present during the same period of the outbreak. We report the occurrence of a novel mutation at 323aa (314aa of orf1b) of nsp12 (RNA-dependent RNA polymerase) changed to phenylalanine (F) from proline (P), in the first reported isolate of SARS-CoV-2, Wuhan-Hu-1. This 323F variant was present at a very high frequency in Northern Nevada. Structural modeling determined this mutation in the interface domain, which is important for the association of accessory proteins required for the polymerase. In conclusion, we report the introduction of specific SARS-CoV-2 variants at very high frequency in distinct geographic locations, which is important for understanding the evolution and circulation of SARS-CoV-2 variants of public health importance, while it circulates in humans.
- SARS-CoV-2,
- COVID-19,
- Genome enrichment,
- nsp12,
- RdRp,
- orf1b 314

These authors contributed equally to this work.

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