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Jumping genes can knock out DNA; alter human genome

ANN ARBOR, MI Results of a new University of Michigan study suggest that junk DNA dismissed by many scientists as mere strings of meaningless genetic code could have a darker side.

In a paper published in the Aug. 9 issue of Cell, scientists from the U-M Medical School report that, in cultured human cancer cells, segments of junk DNA called LINE-1 elements can delete DNA when they jump to a new location possibly knocking out genes or creating devastating mutations in the process.

"The value of this study is the unexpected knowledge that LINE-1 elements have the potential to cause broad-spectrum mutations in individual tumor cells," says John V. Moran, Ph.D., an assistant professor of human genetics and internal medicine in the U-M Medical School.

Transposable LINE-1 or L1 elements make up 17 percent of human DNA, according to Moran, who developed the first assay to identify mobile L1s in the human and mouse genome. L1s "reproduce" by using RNA and a process called reverse transcription to make complementary DNA copies of themselves, as they integrate into other DNA sequences.

"Of 37 transposable events in our study, four resulted in deletions of genetic material," says Nicolas Gilbert, Ph.D., a U-M post-doctoral fellow in human genetics. "One of the deletions was more than 24 Kb in length [24,000 individual units of DNA called nucleotides] and potentially as large as 71 Kb. That's roughly equivalent to the size of BRCA1, a well-known gene that helps prevent the development of breast cancer."

"In cultured cells, we know that L1s can add to the genome by increasing its size, and now we've learned that they can decrease genome size by deleting genetic material," says Sheila Lutz-Prigge, a U-M research associate and co-author of the study. "But we have no control over the size or location of the deletion, and we don't yet know how often it occurs in humans."

Moran and his research team are part of a small group of sci
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Contact: Sally Pobojewski
pobo@umich.edu
734-615-6912
University of Michigan Health System
8-Aug-2002


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