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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1.

Kyle G Rodino1, David R Peaper2, Brendan J Kelly3

  • 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvaniagrid.25879.31, Philadelphia, Pennsylvania, USA.

Journal of Clinical Microbiology
|May 18, 2022
PubMed
Summary
This summary is machine-generated.

Partial ORF1ab gene target failure (pOGTF) on diagnostic assays can rapidly detect the SARS-CoV-2 BA.2.12.1 variant. This molecular marker offers faster variant tracking than sequencing, aiding public health surveillance.

Keywords:
ORF1ab geneRT-PCRSARS-CoV-2cycle threshold (CT) valuepartial ORF1ab gene target failure (pORF1ab)whole-genome sequencing (WGS)

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Area of Science:

  • Virology
  • Molecular Diagnostics
  • Epidemiology

Background:

  • Genomic mutations in SARS-CoV-2 can impact molecular diagnostic assay performance.
  • S-gene target failure has previously served as an indicator for specific SARS-CoV-2 variants.
  • Emerging variants necessitate rapid detection methods to monitor spread and inform public health responses.

Purpose of the Study:

  • To describe partial ORF1ab gene target failure (pOGTF) as a potential indicator for SARS-CoV-2 variants.
  • To evaluate the sensitivity and specificity of pOGTF for detecting SARS-CoV-2 lineage BA.2.12.1.
  • To assess the utility of pOGTF for real-time tracking of variant prevalence.

Main Methods:

  • Utilized cobas SARS-CoV-2 assays to identify partial ORF1ab gene target failure (pOGTF), defined by a ≥2-thermocycle delay in ORF1ab gene detection compared to the E-gene.
  • Compared pOGTF rates with the prevalence of SARS-CoV-2 lineage BA.2.12.1 sequences in public databases.
  • Correlated local pOGTF rates with overall test positivity rates.

Main Results:

  • Partial ORF1ab gene target failure (pOGTF) demonstrated 98.6% sensitivity and 99.9% specificity for SARS-CoV-2 lineage BA.2.12.1.
  • Observed increasing rates of pOGTF closely mirrored the increasing prevalence of BA.2.12.1 sequences.
  • Local pOGTF rates correlated with rising overall SARS-CoV-2 test positivity.

Conclusions:

  • Partial ORF1ab gene target failure (pOGTF) is a sensitive and specific marker for SARS-CoV-2 BA.2.12.1.
  • pOGTF can serve as a rapid proxy for tracking BA.2.12.1 variant spread, outperforming whole-genome sequencing in speed.
  • This method can enhance variant surveillance, particularly for laboratories lacking sequencing capabilities.