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Dolly's Other DNA Came from Donor Egg

Dolly's Other DNA Came from Donor Egg

Janice Hopkins Tanne, New York

The DNA in the nuclei in cells of Dolly, the cloned sheep, came from the udder cell of an adult sheep. But where did the DNA in her mitochondria come from?

A report by scientists from Columbia University College of Physicians and Surgeons in New York and the Roslin Institute in Scotland reveals that all Dolly's mitochondrial DNA came from the enucleated oocyte with which the udder cell was merged (Nature Genetics 1999;23:90-3)

The discovery has implications for preventing the inheritance of rare but fatal human mitochondrial diseases. Although there are only 37 genes in human mitochondrial DNA, these genes control almost all energy metabolism in every human cell. "Without them, we'd be out of business," said Dr Eric Schon, professor of genetics and development in neurology at Columbia.

Dr Schon explained how Dolly was created: "The team at Roslin took the whole udder cell, placed it next to the enucleated egg cell, and ran an electric pulse through. The pulse is thought to punch holes in the membrane, and the nucleus slides into the oocyte."

Almost certainly, some of the udder cell's mitochondrial DNA also got into the oocyte; Dr Schon expected to see perhaps 2-5% of mitochondrial DNA from the udder cell in the mitochrondrial DNA of Dolly.

"We were surprised to find no contribution from the somatic [udder] cell," he told the BMJ.

The explanation for Dolly's lack of udder cell mitochondrial DNA is what Dr Schon thinks happens in humans. Sperm have mitochondria in the neck part of the sperm's tail, but the mitochondria are destroyed after merging with the egg.

Somehow, egg cells get rid of mitochondria carried by sperm. Only maternal mitochondrial DNA is inherited. "Mitochondrial DNA defects are truly devastating. The infants turn into vegetables. They may live only until 15 or 20. There are no animal models, and there's no treatment," Dr Schon said.

A woman with a defect in mitochondrial DNA is likely to see a geneticist only when she has had an affected child. Prenatal diagnosis, available at a few centres, is often inconclusive.

In future, to prevent transmission of a mitochondrial DNA defect, a woman with a defect might choose to have the nucleus from one of her somatic cells merged with an enucleated oocyte from a donor woman with healthy mitochondrial DNA.

[British Medical Journal/September 4, 1999]

Permission granted by British Medical Journal.

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