 Hi, I'm Hank Kazazian. I'm the corresponding author of a recently published paper in Human Mutation entitled Pathogenic Orphan Transduction Created by a Non-Reference Line 1 Retrotranspose on. The senior author of this paper is Sylvia Solium, a postdoc in my laboratory. Now line 1s are present in the human genome in about 500,000 copies, making up some 17% of the genome. However, every human individual has only between 80 and 100 of these elements, which are active. And actually only a handful of those, perhaps 5 to 10, are what we call highly active or hot L1 elements. Approximately a year ago, Awano et al. published a paper that said that there was a 212 base pair single copy sequence that was inserted into the dystrophin gene in an exon of that gene, knocking out the gene and causing Duchenne muscular dystrophy in a Japanese boy. Now, as you know, Duchenne is an X-link disorder, and it turned out that this 212 base pair single copy sequence came from a particular site on chromosome 11. However, when Awano searched the reference genome for this sequence, there was no line 1 element or any other retro transposon nearby this sequence. Now we had known for many years that a sizeable fraction, maybe 10 to 20% of all line 1 insertions, come with 3 prime transductions. A 3 prime transduction is a flanking sequence, which is usually single copy that comes along with the retro transposition of the line 1 element. That's because the poly-A signal of the line 1 is a very weak one, and so the transcript reads through into the flank to the next poly-A signal where the transcript is cut off, and then reverse transcription occurs back and you get the 3 prime flanking sequence along with line 1 sequence in the insertion. However, back in 1999, John Moran and I had postulated that if there was severe 5 prime truncation of the insertion, that there would be no L1 inserted along with the 3 prime flanking sequence. Now, Adam Ewing in the laboratory had worked out this very nice technique to find nearly all human specific L1s in any particular genome. And when he looked at 15 unrelated individuals, he found that one Japanese individual had an L1 insertion, just a couple hundred base pairs upstream on chromosome 11, of this single copy sequence that it inserted into the dystrophin gene. This particular L1 was a full-length L1, and Sylvia Solium found that it had intact open reading frames, was very close to consensus sequence. And when she put it into the cell culture assay, it was highly active or hot, just as active as any previous element that we had run in this assay. The element she found was present in only 6% of Japanese chromosome 11s in that population, and not present at all, as far as we know at this time, in any other ethnic group. So, this is the story of this particular insertion. It turned out it must have been a trans, from a transcript of this particular L1 that went into the 3 prime flank, and only the 3 prime 212 base pairs of single copy sequence along with the poly A tail had been inserted into the dystrophin gene, causing the muscular dystrophy. So, this is what we call an orphan 3 prime transduction. If you have any questions concerning this video, I can be reached at Kazazian, that's k-a-z-a-z-i-a-n, at j-h-m-i dot edu. I welcome your comments and further questions. I'd also like to tell you that I've recently published a book on mobile DNA, Finding Treasure and Junk, referring to junk DNA, and this book contains more information about the mobile DNA field and about the graduate students and postdocs who have done the work in this area in my laboratory. Thanks for your attention.