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Identification of mobile retrocopies during genetic testing: Consequences for routine diagnosis
Author(s) -
Chatron Nicolas,
Cassinari Kevin,
Quenez Olivier,
BaertDesurmont Stéphanie,
Bardel Claire,
Buisine MariePierre,
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,
RollatFarnier PierreAntoine,
Simonet Thomas,
SaugierVeber Pascale,
Tabet AnneClaude,
Toutain Annick,
Wilkie Andrew O. M.,
Lesca Gaetan,
Sanlaville Damien,
Nicolas Gaël,
SchluthBolard Caroline
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23845
Subject(s) - biology , indel , genetics , exon , exome sequencing , intron , genome , human genome , computational biology , exome , alu element , locus (genetics) , retrotransposon , mobile genetic elements , dna sequencing , gene , genetic testing , transposable element , mutation , single nucleotide polymorphism , genotype
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.