Dolly Not a Complete Clone

N E W   Y O R K,   Sept. 7, 2001 -- A study confirms what scientists had always thought about Dolly the sheep: If you want to be really picky, you can say she’s not completely identical genetically to the ewe she was cloned from.

No need to rewrite the textbooks: The finding doesn’t change Dolly’s status as the first animal to be cloned from an adult mammal.

When most people think about genes, they think of the DNA in the nucleus of the cell. The genes there control a wide variety of characteristics like eye color. And for this DNA, Dolly is indeed a clone.

Differences in the Mitochondria

But cells contain a much smaller amount of DNA outside the nucleus, in features called mitochondria. The mitochondria are the power plants of cells, and their DNA — called mtDNA — controls their functioning.

This mtDNA accounts for about 1 percent of a typical cell’s DNA and a much smaller percentage of its genes.

Scientists always thought that Dolly’s mtDNA would differ from the mtDNA in the ewe she was cloned from. Dolly was cloned by fusing a body cell from the ewe to an egg that had its nucleus removed. A body cell has far less mtDNA than an egg does, so when they mixed, the vast majority of the result would be from the egg.

Ewe Not Even Involved

Now, scientists have inspected Dolly’s mtDNA and found no trace of the ewe’s contribution at all. That’s a surprise, and it suggests the egg destroyed the ewe’s mtDNA, said Eric Schon of the Columbia University College of Physicians and Surgeons in New York.

He and colleagues present the results in the September issue of the journal Nature Genetics. Co-authors include Dolly cloner Ian Wilmut of the Roslin Institute in Scotland.

They got the same result with the mtDNA of nine sheep cloned from fetal cells.

Schon said the work has a big implication for attempts to study diseases caused by flaws in mtDNA. Only a small minority of genetic diseases are caused by such flaws, with far more stemming from defects in nucleus DNA.

Defects Could Cause Diseases But defects in mtDNA cause a variety of devastating diseases, most of them very rare, with such outcomes as blindness, deafness, mental retardation and difficulty walking. Defective mtDNA may also cause some 2 percent of adult-onset diabetes, Schon said.

Scientists now have trouble studying mtDNA diseases because they can’t reproduce the human disorders in animals, Schon said. One idea has been to grow mitochondria with defective mtDNA in the laboratory and inject them into egg cells, with the idea of producing mice that carry the defective mtDNA.

But the new work suggests that might not succeed, because the egg might destroy the foreign mitochondria, Schon said. The new report is “a wake-up call to us” to figure out ways to block that destruction, he said.