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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Mutations on COVID-19 diagnostic targets.

Rui Wang1, Yuta Hozumi1, Changchuan Yin2

  • 1Department of Mathematics, Michigan State University, MI 48824, USA.

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Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affect current COVID-19 diagnostic tests. The nucleocapsid (N) gene shows the most mutations, impacting diagnostic reliability and necessitating new target selection.

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Area of Science:

  • Virology
  • Genomics
  • Molecular Biology

Background:

  • Effective diagnostic reagents are crucial for managing the COVID-19 pandemic.
  • Current diagnostic tests for SARS-CoV-2 may be compromised by viral mutations.
  • Lack of vaccines and specific treatments highlights the need for reliable diagnostics.

Purpose of the Study:

  • To analyze mutations in SARS-CoV-2 genome samples to assess their impact on diagnostic reagents.
  • To identify highly mutated genes in SARS-CoV-2, particularly those targeted by diagnostic tests.
  • To guide the selection of conservative genes for developing improved COVID-19 diagnostic tools, vaccines, and therapeutics.

Main Methods:

  • Genotyping of 31,421 SARS-CoV-2 genome samples collected up to July 23, 2020.
  • Computation of mutation rates and mutation h-index for all SARS-CoV-2 genes.
  • Analysis of mutation patterns, including APOBEC mRNA editing (C > T).

Main Results:

  • Nearly all current COVID-19 diagnostic targets have accumulated mutations.
  • The nucleocapsid (N) gene exhibits the highest mutation frequency and is identified as a non-conservative gene.
  • APOBEC-induced C > T editing influences mutation patterns, suggesting avoidance of cytidines in target selection.

Conclusions:

  • The high mutation rate in the SARS-CoV-2 N gene compromises the accuracy of existing diagnostic reagents.
  • Selection of diagnostic targets should consider mutation rates and avoid cytidine-rich regions.
  • Findings support the development of more robust COVID-19 diagnostics, vaccines, and therapeutics by targeting conserved viral regions.