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The code presented here was used to discover and characterize a novel overlapping ORF in the mRNA of POLG (ORF-Y) and a second, further upstream ORF (ORF-Z) that is likely regulatory in modulating translation between ORF-Y and the main ORF. The work is of interest for two main reasons
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Overlapping ORFs in the human genome of such length are extremely rare. ORF-Y in POLG may represent the longest bonafide overlapping ORF in the human genome.
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POLG is of significant clinical relevance. Many mutations have been mapped across its mRNA that link to mitochondrial disease. Given the extent of overlap with ORF-Y, it is possible that the mechanism of action of some of these mutations is a combined effect exerted on both the protein products of main ORF and ORF-Y.
The following will cogently run the readers through how the analysis of each of the figures was conducted with the accompanying code.