Identification of mobile retrocopies during genetic testing: Consequences for routine diagnosis.

Hum Mutat 2019 Jun 23. Epub 2019 Jun 23.

Genetics Department, Hospices Civils de Lyon, Lyon, France.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23845DOI Listing
June 2019
5 Reads

Publication Analysis

Top Keywords

genetic testing
12
called read
4
read alignment
4
gain called
4
number gain
4
exons-only copy
4
copy number
4
alignment inspection
4
inspection revealed
4
shift exon-intron
4
exon-intron junction
4
coverage shift
4
depth coverage
4
cases exons-only
4
revealed depth
4
junction indels
4
sequencing cases
4
retrocopies detected
4
detected diagnostic
4
observations retrocopies
4

References

(Supplied by CrossRef)
Detection of exon deletions and duplications of the mismatch repair genes in hereditary nonpolyposis colorectal cancer families using multiplex polymerase chain reaction of short fluorescent fragments
Charbonnier F. et al.
Cancer Research 2000

Similar Publications