Possible Telomere Shortening in Clones

James Ganong (JGanong@webtv.net)
Thu, 27 May 1999 00:09:33 -0700 (PDT)

Scientists: Cloned sheep Dolly has 'old' DNA May 26, 1999
Web posted at: 6:10 p.m. EDT (2210 GMT)
LONDON (Reuters) -- Scientists who created Dolly the sheep, the world's first mammal cloned from an adult cell, said Wednesday she has slight DNA damage that could have an impact on how cloning technology is used in the future.
Dolly and two other cloned sheep have shorter telomeres -- the tiny strands of DNA at the end of chromosomes that scientists believe may hold the secrets to youth and aging.
Telomeres shorten each time a cell divides and are progressively eroded as an animal ages. As the telomeres shorten the chromosomes can become unstable and prone to damage.
Researchers from Edinburgh's Roslin Institute and PPL Therapeutics said Dolly, who was cloned from a cell taken from a 6-year-old sheep, had telomeres that were about 20 percent shorter than those of other sheep of a similar age.
"We don't see any signs of any problem in Dolly and the other animals
but perhaps it is too early to note such a problem. We just don't know," PPL's Alan Colman said in an interview. The finding, reported in a letter to the science journal Nature, is not unexpected. Scientists know that cell culture leads to a shortening of telomeres and cells used for Dolly and the other sheep were cultured in the laboratory.
In Dolly's case the shortening was compounded because she was derived from a cell from a middle-aged animal.
"This telomere erosion is just one form of DNA damage. People have
speculated for years that as we get older our cells accumulate mutations individually. When you make an animal from one of those cells it is possible that you are transferring that," Colman said. Although the research does not appear to have any consequences for cloning livestock it could have implications in other uses of the technology.
"It reminds people this is an issue that should be called into account
in any of the proposals for, not so much agricultural cloning, but some of the uses in human therapeutic cloning where extensive time periods of culture in vitro would be necessary. It could be an issue," he added. Therapeutic cloning to improve treatments for serious diseases such as Alzheimer's and Parkinson's or to create cloned tissue and organs would involve the use of adult cells. "Human therapeutic cloning, if it ever does come about, is going to use human adult cells. That's the whole purpose," said Colman.
The research could be particularly important in sequential cloning -- cloning a clone of a clone -- which could lead to progressive shortening of telomeres.
But Coleman and his colleagues said problems, if they do arise, may not be insurmountable. Scientists can use embryonic cells for cloning and could also cut the cell time in culture which could reduce telomere shortening.