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It May Take A Mouse To Understand The Behavior Of "Jumping Genes"

Date:
December 4, 2002
Source:
University Of Pennsylvania Medical Center
Summary:
Researchers at the University of Pennsylvania School of Medicine have bred a mouse to model human L1 retrotransposons, the so-called "jumping genes." Retrotransposons are small stretches of DNA that are copied from one location in the genome and inserted elsewhere, typically during the genesis of sperm and egg cells. The L1 variety of retrotransposons, in particular, are responsible for about one third of the human genome.

Philadelphia, PA –Researchers at the University of Pennsylvania School of Medicine have bred a mouse to model human L1 retrotransposons, the so-called "jumping genes." Retrotransposons are small stretches of DNA that are copied from one location in the genome and inserted elsewhere, typically during the genesis of sperm and egg cells. The L1 variety of retrotransposons, in particular, are responsible for about one third of the human genome.

The mouse model of L1 retrotransposition is expected to increase our understanding of the nature of jumping genes and their implication in disease. According to the Penn researchers, the mouse model may also prove to be a useful tool for studying how a gene functions by knocking it out through L1 insertion. Their report is in the December issue of Nature Genetics and currently available online (see below for URL).

"There are about a half million L1 sequences in the human genome, of which 80 to 100 remain an active source of mutation," said Haig H. Kazazian, Jr., MD, Chair of Penn's Department of Genetics and senior author in the study. "This animal model will help us better understand how this happens, as well as provide a useful tool for discovering the function of known genes."

In humans, retrotransposons cause mutations in germ line cells, such as sperm, which continually divide and multiply. Like an errant bit of computer code that gets reproduced and spread online, retrotransposons are adept at being copied from one location and placed elsewhere in the chromosomes. When retrotransposons are inserted into important genes, they can cause disease, such as hemophilia and muscular dystrophy. On the other hand, retrotransposons have been around for 500 to 600 million years, and have contributed a lot to evolutionary change.

"In the grand scheme of evolution, retrotransposons have behaved like fickle gods, arbitrarily wreaking havoc in some and benefiting others," said Kazazian. "Retrotransposons can cause new genes to emerge that may benefit an organism – or they can kill by knocking out important genes. Overall, however, it seems that they are neutral and add to the apparent sloppiness of the genome."

For some time, researchers have been trying to understand how retrotransposons affect the genome and, in addition, what science may learn from the techniques they employ. According to Kazazian and his colleagues, the mouse model displays high-frequency chromosome to chromosome retrotransposition of human L1s, which behave in exactly the same way as they do in humans. While the current tissue culture model works well, it does not mimic the way retrotransposons jump in chromosomes.

The researchers believe that by understanding the mechanics of retrotransposition, they might be able to use similar techniques for genetic therapies in humans. They also hope to learn more about the basic mysteries behind retrotransposition, such as why L1 retrotransposons only seem to effect the germ line and not any other type of cell in the body.

As science refines the content of the mouse genome database, Kazazian foresees that this model will also be useful for determining the function of different genes. As new genes are identified, their purpose can be resolved by using retrotransposons to knock them out of commission. "Such knowledge has direct impact in humans," said Kazazian, "Information important to determining the nature of human diseases and developing new therapeutics can be extrapolated from our knowledge of the mouse genome."


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "It May Take A Mouse To Understand The Behavior Of "Jumping Genes"." ScienceDaily. ScienceDaily, 4 December 2002. <www.sciencedaily.com/releases/2002/12/021204081310.htm>.
University Of Pennsylvania Medical Center. (2002, December 4). It May Take A Mouse To Understand The Behavior Of "Jumping Genes". ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2002/12/021204081310.htm
University Of Pennsylvania Medical Center. "It May Take A Mouse To Understand The Behavior Of "Jumping Genes"." ScienceDaily. www.sciencedaily.com/releases/2002/12/021204081310.htm (accessed October 22, 2014).

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