Abstract
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 fulllength 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.
Original language | English (US) |
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Pages (from-to) | 369-371 |
Number of pages | 3 |
Journal | Human mutation |
Volume | 33 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2012 |
Externally published | Yes |
Keywords
- 3'transduction
- Duchenne muscular dystrophy
- Dystrophin
- Line-1
- Retrotransposon
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)