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Mitochondrial DNA and the Rhesus monkeys

Date: 18.9.2009 

Scientists may have found a way to prevent the transfer of serious inherited mitochondrial diseases from mother to child. By shuttling DNA from an egg cell to a donor cell, the technique enabled the birth of four healthy Rhesus monkey males, researchers report online August 26 in Nature.
Mitochondria, power-producing organelles in cells, carry their own DNA, distinct from the DNA held in cells' nuclei. Healthy or otherwise, mitochondrial DNA is passed from mother to child. In recent years, researchers have identified more than 150 harmful mutations in mitochondrial DNA, some of which can cause serious and debilitating diseases.

Some estimates report that 1 in 6,000 people may have inherited a mitochondrial DNA disorder. Other estimates put the number higher, Wallace says.
A single cell can have thousands of copies of mitochondrial DNA. Usually, all of these copies are the same, healthy type, but occasionally a cell can have a mixture of normal and mutant mitochondrial DNA, a condition called heteroplasmy.

Heteroplasmy in an egg cell makes it nearly impossible to determine if a baby is going to inherit a severe mitochondrial disease, says Jo Poulton of the University of Oxford in England. "You can get quite a big range of how much mitochondrial DNA is transferred to children. There's been a lot of debate on whether you can or can't do genetic counseling" for these women, she says.

To get around the guesswork surrounding inherited mitochondrial diseases, the researchers took the mother's mitochondrial DNA completely out of the picture. In the new work, researchers identified nuclear DNA in a mother's egg cell by the DNA's attachment to structures called spindles. Researchers removed the nuclear DNA (leaving the original mitochondrial DNA behind) and then put it into different egg cells lacking nuclear DNA but replete with healthy donor mitochondrial DNA. With the help of an inactive virus, the nuclear DNA fused into the donor cells.

Next, these modified egg cells were fertilized with donor sperm and implanted into Rhesus females to develop. Male twins, named Mito and Tracker, were born healthy, followed later by two more individual males, named Spindler and Spindy, from different mothers.

Researchers found no traces of the original egg cell's mitochondrial DNA in the offspring, indicating that the process successfully prevented its transfer.
The researchers used Rhesus monkey mothers with no mitochondrial DNA mutations because there are no established primate groups with such mutations, Mitalipov says. However, genetic signatures from the two cell groups-the mother and the egg donor-were distinct enough to tell apart easily, he adds.

"We'd like to see the growth and development of the offspring, to see if they have any abnormalities," he says. Doing that, though, will require female offspring, since mitochondria are passed on maternally. Mitalipov says they are now trying for a girl.

Wallace says that the virus used to integrate the nuclear DNA into a donor cell would need to be scrutinized for safety. The virus is "something FDA would look at very carefully," before approving the procedure, he says. What's more, no one knows what will happen as the monkeys get older.
Poulton points out that techniques like this performed in animals might not reveal subtle defects, such as the mild hearing loss associated with some mitochondrial DNA mutations.

Autor: Dina Velichová







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