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Cloned animals don't look alike
Posted: Saturday, December 28, 2002
Author: Tina Hesman Post-Dispatch
Filed: 12/28/2002, 10:36:21 PM
Source: St. Louis Post-Dispatch
Cloned animals may be exact copies genetically, but they don't look alike
When scientists at Clonaid announced Friday that they have successfully cloned a human being, many researchers expressed skepticism. But even if the baby girl is a genetic replica of her mother, the child is likely to look different from the woman who spawned her and behave differently, experts say. And the human clone could be at risk for a myriad of health problems such as those seen in cloned animals.
Scientists must make multiple attempts to produce clones. For every clone produced, many more die in the test-tube or during gestation, and scientists don't yet understand why or what to do about it.
"We have ideas about what the root causes are, but we don't have any idea about how to fix it," said Randall Prather, a reproductive biologist at the University of Missouri in Columbia. Prather has cloned pigs in a project that aims at producing organs for transplant into humans.
Although the pigs are genetic carbon copies of one another, the animals have differences in appearance, Prather said. Some pigs are taller than others or have different markings, he said.
Those differences are probably not due to changes in the animals' DNA, Prather said. He attributes the differences among his pigs and other cloned animals to imprinting - modifications to DNA that affect how genes are turned on and off.
Every cell in an animal's (or person's) body contains a complete set of genes for making the organism. But just as parents need instructions for assembling bicycles from a jumble of parts, so people and animals need directions for building bodies. Imprinting provides some of those directions.
That imprinting makes an impression that can last through all the manipulations of cloning. If imprinting is not fully erased, a cloned animal may have abnormalities.
Cloned mice often become obese in old age.
Dolly the sheep, the first animal cloned by nuclear transfer, is pudgy and arthritic.
Some cloned animals can't straighten their legs fully because their tendons contract.
Other cloned animals have weakened immune systems or enlarged hearts.
The most obvious evidence that clones aren't exact replicas of their genetic donors is CC, a cat cloned by scientists at Genetic Savings and Clone in College Station, Texas. The researchers took the genetic information used to make CC from a calico cat called Rainbow. The cats look completely different despite their identical genetic makeup. Rainbow's coat is splotched with orange and black patches, but CC is a black and white tiger tabby.
The researchers who created CC say that her mysterious lack of orange spots could be due to a failure to reset a type of imprinting known as X-linked inactivation.
Female cats, humans and other mammals have two X-chromosomes. Males carry only one X-chromosome and one Y-chromosome. To balance what would otherwise be a double dose of X genes, one of the X-chromosomes in each cell of a female animal's body is inactivated. The process seems to be completely random.
In humans, the effect is not usually noticeable, but in cats, X-inactivation affects a gene that controls coat color. One variant of the gene makes the fur orange, another version of the gene produces black fur. In calico cats, the X-chromosome containing the orange version of the gene gets shut off in some spots. That means the X-chromosome with the black gene is still active in those patches and produces splotches of black fur. In other spots, the X-chromosome containing the black gene is inactivated, producing orange patches.
Since CC has no orange fur, the researchers speculate that her genetic material was taken from a cell in which the X-chromosome carrying the orange gene was shut off. That leaves the year-old cat with only black patches, but indicates that CC could have other problems with her genetic programming.
Because humans also inactivate X-chromosomes, a cloned baby girl might have a similar problem. Experiments with cloned mice showed no defect in resetting inactive X-chromosomes, but the mice did have other differences in gene regulation.
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