These authors contributed equally to this work and should be considered joint first authors.
Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon†
Article first published online: 8 DEC 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 2, pages 369–371, February 2012
How to Cite
Solyom, S., Ewing, A. D., Hancks, D. C., Takeshima, Y., Awano, H., Matsuo, M. and Kazazian, H. H. (2012), Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon. Hum. Mutat., 33: 369–371. doi: 10.1002/humu.21663
Communicated by Mark H. Paalman
- Issue published online: 12 JAN 2012
- Article first published online: 8 DEC 2011
- Accepted manuscript online: 17 NOV 2011 05:55PM EST
- Manuscript Accepted: 10 NOV 2011
- Manuscript Received: 20 SEP 2011
- NIH. Grant Number: RC4MH092880 to H.H.K
- 3′ transduction;
- Duchenne muscular dystrophy
Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17% of the human genome, and move by a potentially mutagenic “copy and paste” mechanism via an RNA intermediate. Recently, the retrotransposition-mediated insertion of a new transcript was described as a novel cause of genetic disease, Duchenne muscular dystrophy, in a Japanese male. The inserted sequence was presumed to derive from a single-copy, noncoding RNA transcribed from chromosome 11q22.3 that retrotransposed into the dystrophin gene. Here, we demonstrate that a nonreference full-length LINE-1 is situated in the proband and maternal genome at chromosome 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene. This LINE-1 is highly active in a cell culture assay. LINE-1 insertions are often associated with 3′ transduction of adjacent genomic sequences. Thus, the likely explanation for the mutagenic insertion is a LINE-1-mediated 3′ transduction with severe 5′ truncation. This is the first example of LINE-1-induced human disease caused by an “orphan” 3′ transduction. Hum Mutat 33:369–371, 2012. © 2011 Wiley Periodicals, Inc.