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Missing steps of jumping-gene replication discovered

In experiments with transgenic mice, University of Pennsylvania School of Medicine researchers discovered the remaining steps in the complicated process of how the largest class of jumping genes replicates and inserts themselves within the human genome. Haig H. Kazazian, Jr. MD, Chair of the Department of Genetics, and colleagues at Penn published their findings in the February issue of Genome Research. This knowledge may shed light on the origins of "junk" DNA, parts of the genome for which no function has yet been discovered.

Jumping genesalso called mobile DNA or transposonsare sequences of DNA that can move or jump to different areas of the genome within the same cell. They are a rare cause of several genetic diseases, such as hemophilia and Duchenne muscular dystrophy.

Retrotransposons are one class of jumping genes, with the L1 family being the most abundant in the human genome. Retrotransposons move by having their DNA sequence transcribed or copied to RNA, and then instead of the genetic code being translated directly into a protein sequence, the RNA is copied back to DNA by the retrotransposon's own enzyme called reverse transcriptase. This new DNA is then inserted back into the genome. This process of copying is similar to that of retroviruses, such as HIV, leading scientists to speculate about a viral origin for retrotransposons.

"L1 retrotransposons, which are the only active mobile DNA elements in humans, have accounted for about 30 percent of the human genome by their own insertions and by driving the insertion of other kinds of elements," says Kazazian. "In fact, humans have over 500,000 L1 retrotransposons within an individual genome."

In order to learn about the effects of L1 retrotransposon insertions into the human genome, the researchers made a transgenic mouse in which human L1 retrotransposons could replicate. They injected several copies of a human L1 retrotransposon to create the transgenic mouse. In subsequ
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
31-Jan-2006


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