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Processed pseudogene insertions in somatic cells.

Kazazian HH - Mob DNA (2014)

Bottom Line: Processed pseudogenes are copies of messenger RNAs that have been reverse transcribed into DNA and inserted into the genome using the enzymatic activities of active L1 elements.Until recently, very few polymorphic processed pseudogenes had been discovered in mammalian genomes.Now several studies have found a number of polymorphic processed pseudogenes in humans.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

ABSTRACT
Processed pseudogenes are copies of messenger RNAs that have been reverse transcribed into DNA and inserted into the genome using the enzymatic activities of active L1 elements. Processed pseudogenes generally lack introns, end in a 3' poly A, and are flanked by target site duplications. Until recently, very few polymorphic processed pseudogenes had been discovered in mammalian genomes. Now several studies have found a number of polymorphic processed pseudogenes in humans. Moreover, processed pseudogenes can occur in somatic cells, including in various cancers and in early fetal development. One recent somatic insertion of a processed pseudogene has caused a Mendelian X-linked disease, chronic granulomatous disease.

No MeSH data available.


Related in: MedlinePlus

Orientation of the TMF1 insertion in intron 1 of the CyBB gene (below), leading to an extra exon between exons 1 and 2 in the CYBB mRNA (above). Republished with permission from Human Mutation published by Wiley.
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Figure 2: Orientation of the TMF1 insertion in intron 1 of the CyBB gene (below), leading to an extra exon between exons 1 and 2 in the CYBB mRNA (above). Republished with permission from Human Mutation published by Wiley.

Mentions: There are three interesting aspects of this case. First, the insertion was a semi-processed pseudogene of the TMF1 (TATA element modulatory factor) gene from chromosome 3 that had inserted into intron 1 of CYBB in reverse orientation. A PP had not been observed previously as a new insertion among 100 previous insertions (L1, Alu, SVA) in human Mendelian disease or cancer etiology [32]. Interestingly, TMF1 is one of the about 10% of human genes that is represented by a single PP in the human reference genome sequence [14]. Second, the insertion was 3’ truncated and contained exons 1 to 8 of TMF1 along with intron 7 and much of intron 8. Transcription of TMF1 had terminated after an alternative poly A signal, AGUAAA, in intron 8, and a 100 bp poly A tail was added to the transcript. After insertion of this semi-processed pseudogene in reverse orientation into intron 1 of CYBB, splicing had occurred into an excellent acceptor splice site and out of an excellent donor site in exon 2 of TMF1. The newly created 117 bp exon also contained a nonsense codon that caused the CYBB gene to be non-functional (Figure 2). Finally, the PP insertion had occurred during early embryonic development of the patient’s mother. Roughly 10% to 20% of her lymphocytes contained the insertion as shown by qPCR.


Processed pseudogene insertions in somatic cells.

Kazazian HH - Mob DNA (2014)

Orientation of the TMF1 insertion in intron 1 of the CyBB gene (below), leading to an extra exon between exons 1 and 2 in the CYBB mRNA (above). Republished with permission from Human Mutation published by Wiley.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4151081&req=5

Figure 2: Orientation of the TMF1 insertion in intron 1 of the CyBB gene (below), leading to an extra exon between exons 1 and 2 in the CYBB mRNA (above). Republished with permission from Human Mutation published by Wiley.
Mentions: There are three interesting aspects of this case. First, the insertion was a semi-processed pseudogene of the TMF1 (TATA element modulatory factor) gene from chromosome 3 that had inserted into intron 1 of CYBB in reverse orientation. A PP had not been observed previously as a new insertion among 100 previous insertions (L1, Alu, SVA) in human Mendelian disease or cancer etiology [32]. Interestingly, TMF1 is one of the about 10% of human genes that is represented by a single PP in the human reference genome sequence [14]. Second, the insertion was 3’ truncated and contained exons 1 to 8 of TMF1 along with intron 7 and much of intron 8. Transcription of TMF1 had terminated after an alternative poly A signal, AGUAAA, in intron 8, and a 100 bp poly A tail was added to the transcript. After insertion of this semi-processed pseudogene in reverse orientation into intron 1 of CYBB, splicing had occurred into an excellent acceptor splice site and out of an excellent donor site in exon 2 of TMF1. The newly created 117 bp exon also contained a nonsense codon that caused the CYBB gene to be non-functional (Figure 2). Finally, the PP insertion had occurred during early embryonic development of the patient’s mother. Roughly 10% to 20% of her lymphocytes contained the insertion as shown by qPCR.

Bottom Line: Processed pseudogenes are copies of messenger RNAs that have been reverse transcribed into DNA and inserted into the genome using the enzymatic activities of active L1 elements.Until recently, very few polymorphic processed pseudogenes had been discovered in mammalian genomes.Now several studies have found a number of polymorphic processed pseudogenes in humans.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

ABSTRACT
Processed pseudogenes are copies of messenger RNAs that have been reverse transcribed into DNA and inserted into the genome using the enzymatic activities of active L1 elements. Processed pseudogenes generally lack introns, end in a 3' poly A, and are flanked by target site duplications. Until recently, very few polymorphic processed pseudogenes had been discovered in mammalian genomes. Now several studies have found a number of polymorphic processed pseudogenes in humans. Moreover, processed pseudogenes can occur in somatic cells, including in various cancers and in early fetal development. One recent somatic insertion of a processed pseudogene has caused a Mendelian X-linked disease, chronic granulomatous disease.

No MeSH data available.


Related in: MedlinePlus