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Wistar scientists add difficult-to-sequence stretches to human genome data

Philadelphia - In a new study, researchers at The Wistar Institute report extending the working draft sequence of the human genome to reach most of the tips of human chromosomes, called telomeres. The telomeres and adjacent regions were not fully included in the working draft sequence announced last summer because they have unique properties that make them particularly difficult to isolate and analyze.

In addition, the Wistar researchers found that the adjacent, or subtelomeric regions, appear to display more variation from individual to individual than other parts of the genome. They also reported that the subtelomeric regions are gene-rich, suggesting that these areas may serve essential functions and are not simply buffers of nonfunctional "junk DNA" next to the telomere, as some have thought.

Their study was published in the February 15 Nature, a special issue focusing on the Human Genome Project in which the publicly funded International Human Genome Sequencing Consortium's working draft sequence is published.

"Telomeres and subtelomeric regions make up less than 1 percent of the human genome, but they're quite important," says Harold C. Riethman, Ph.D., lead author on the study and associate professor at The Wistar Institute. "When the cellular machinery that maintains telomeres becomes damaged, a cell fails to divide properly, which is one of the hallmarks of cancer."

In addition to cell division, telomeric DNA mediates many important biological activities, such as cellular aging, movement and localization of chromosomes within the nucleus, and transcriptional regulation of subtelomeric genes.

To analyze the telomeric regions, the researchers developed a specialized yeast cloning vehicle-called half-YAC, or half-yeast artificial chromosome-to produce copies of human DNA regions linked to telomeres. Cloning, or making copies of, DNA is an important step in genomic sequencing. The working draft sequence was produced using a bacteria
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Contact: Marion Wyce
wyce@wistar.upenn.edu
215-898-3943
The Wistar Institute
10-Feb-2001


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