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Therapeutic Cloning Gets A Boost With New Research Findings

ScienceDaily (Mar. 26, 2009) - Germ cells, the cells which give rise to a 
mammal's sperm or eggs, exhibit a five to ten-fold lower rate of spontaneous 
point mutations than adult somatic cells, which give rise to the body's 
remaining cell types, tissues and organs. Despite their comparatively higher 
mutation rates, however, adult somatic cells are used as the donor cells in 
a cloning process called somatic cell nuclear transfer (SCNT). This made 
researchers wonder if cloning by SCNT leads to progeny with more mutations 
than their naturally conceived counterparts. Also, would cloned fetuses 
receive DNA programming predisposing them to develop mutations faster than 
natural fetuses of the same age?
Those scenarios are simply not likely, say researchers at The University of 
Texas at San Antonio, The University of Texas Health Science Center at San 
Antonio and The University of Hawaii at Honolulu's John A. Burns School of 
Medicine. The team, which spent more than five years analyzing mutation 
rates and types in cloned Big BlueŽ mouse fetuses recently published its 
findings in the online Early Edition of the Proceedings of the National 
Academy of Sciences in a paper titled "Epigenetic regulation of genetic 
integrity is reprogrammed during cloning."

The paper offers the first direct demonstration that cloning does not lead 
to an increase in the frequency of point mutations.

John McCarrey, professor of cellular and molecular biology at UTSA and the 
study's principal investigator, suggests a "bottleneck effect" is partially 
responsible for the observations his team recorded. "To create a cloned 
fetus by somatic cell nuclear transfer, only one adult somatic cell -- one 
donor cell -- is needed," he explains. "Because a random cell population 
exhibits a low mutation rate overall and only one cell from that population 
is used for cloning, the likelihood is remote that the cell chosen to be 
cloned will transfer a genetic mutation to its cloned offspring. Therefore, 
the bottleneck effect limits the transfer of mutations from donor cells to 
cloned offspring."

Not only did the researchers find that SCNT does not lead to an increase in 
the frequency of point mutations in cloned mice, the team also found that 
naturally conceived fetuses and cloned fetuses that are the same age have 
similar rates of spontaneous mutation development. They attribute this 
finding to epigenetic reprogramming.

It is known in the scientific community that germ cells contain an 
epigenome, a programmed state of the genome, that keeps mutation rates low. 
They suggest this type of epigenome is found in germ cells because those 
cells are responsible for contributing genetic information to subsequent 
generations. Adult somatic cells (the donor cells in SCNT) have higher 
mutation rates and less stringent epigenetic programming to avoid mutations 
than germ cells, but offspring produced from somatic cells by cloning have 
mutation rates similar to those in offspring produced by natural 
reproduction, suggesting that the epigenome of an adult somatic cell is 
reprogrammed during cloning to maintain the genetic integrity of that cell's 
progeny.

Journal reference:
Patricia Murphey, Yukiko Yamazaki, C. Alex McMahan, Christi A. Walter, Ryuzo 
Yanagimachi, and John R. McCarrey. Epigenetic regulation of genetic 
integrity is reprogrammed during cloning. Proceedings of the National 
Academy of Sciences, 2009; 106 (12): 4731 DOI: 10.1073/pnas.0900687106
Adapted from materials provided by University of Texas at San Antonio, via 
EurekAlert!, a service of AAAS.

Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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