Identification of mobile retrocopies during genetic testing: Consequences for routine diagnosis. Issue 11 (12th July 2019)

• Record Type: Journal Article
• Authors: Chatron, Nicolas; Cassinari, Kevin; Quenez, Olivier; Baert‐Desurmont, Stéphanie; Bardel, Claire; Buisine, Marie‐Pierre; Calpena, Eduardo; Capri, Yline; Corominas Galbany, Jordi; Diguet, Flavie; Edery, Patrick; Isidor, Bertrand; Labalme, Audrey; Le Caignec, Cedric; Lévy, Jonathan; Lecoquierre, François; Lindenbaum, Pierre; Pichon, Olivier; Rollat‐Farnier, Pierre‐Antoine; Simonet, Thomas; Saugier‐Veber, Pascale; Tabet, Anne‐Claude; Toutain, Annick; Wilkie, Andrew O. M.; Lesca, Gaetan; Sanlaville, Damien; Nicolas, Gaël; Schluth‐Bolard, Caroline
• Is Part Of: Human mutation. Volume 40:Issue 11(2019)
• Page Start: 1993
• Page End: 2000
• Publication Date: 2019-07-12
• Subjects: copy number gain -- genetic testing pitfalls -- genome mobility -- retrocopies; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23845
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: Human retrocopies, that is messenger RNA transcripts benefitting from the long interspersed element 1 machinery for retrotransposition, may have specific consequences for genomic testing. Next genetration sequencing (NGS) techniques allow the detection of such mobile elements but they may be misinterpreted as genomic duplications or be totally overlooked. We report eight observations of retrocopies detected during diagnostic NGS analyses of targeted gene panels, exome, or genome sequencing. For seven cases, while an exons‐only copy number gain was called, read alignment inspection revealed a depth of coverage shift at every exon‐intron junction where indels were also systematically called. Moreover, aberrant chimeric read pairs spanned entire introns or were paired with another locus for terminal exons. The 8th retrocopy was present in the reference genome and thus showed a normal NGS profile. We emphasize the existence of retrocopies and strategies to accurately detect them at a glance during genetic testing and discuss pitfalls for genetic testing. Abstract : After paired‐end sequencing, a unique association of exons‐only duplication clustered structural variation calls and aberrant splice site indels at every exon‐intron junctions is the signature of a retrocopy. Such an event shall not be overlooked as they can be pathogenic through a variety of mechanisms related to its insertion site or to its own characteristics. It could also yield false results for other molecular genetics techniques.