Processed pseudogenes arise in the human genome due to retrotransposition events, during which mRNA transcripts are reverse-transcribed and integrated back into the genome. This additional genetic material generally consists of coding sequences, without introns and promoter regions. Pseudogenes are generally considered to be non-functional and rarely cause genetic disease unless inserted into a genomic location which disrupts gene function. Due to mapping and annotation issues with homologous sequence to parent genes, the presence of processed pseudogenes as well as pseudogenes more broadly may lead to false attribution of a genetic variant in a pseudogene to the parent gene, and therefore false-positive results. In our laboratory, we have observed complications during data analysis in both somatic and germline genetic testing due to the presence of processed pseudogenes. In the clinical diagnostic setting, SMAD4 , SETD2 and B2M processed pseudogenes complicate the interpretation of both tumour comprehensive genomic profiling (CGP) and germline multiplex ligation-dependent probe amplification (MLPA) results, creating the risk of incorrectly reporting a clinically significant copy number variant in these genes. Here we present a case series demonstrating the effect of processed pseudogenes, highlighting the importance of pseudogene-informed interpretation when analysing genomic data.
Spina et al. (Sun,) studied this question.