Geneticists discuss mitochondrial transfer


mitochondria_cellcourtesy

A mouse cell embryo and pronuclei, or the nucleus of a sperm or egg cell, is magnified. COURTESY OF KAREN SCHINDLER


No treatments exist for mitochondrial disorders, said Karen Schindler, an assistant professor in the Department of Genetics.

Mitochondrial disorders are diseases that can affect various areas of the body, including but not limited to the brain, kidney, muscles, heart and eyes, according to the Centers for Disease Control and Prevention.

The House of Commons in the United Kingdom recently approved a bill that would allow for parents to use a donor’s egg to prevent mitochondrial DNA mutations from being passed down to children. The procedure is banned in the United States.

“The donor is a cytoplasmic host, because that’s where the mitochondria is,” she said. “Mitochondria are only inherited through the maternal line.”

The process works by extracting DNA from an intended mother’s egg and placing it into an egg with healthy mitochondria, she said. Both eggs would be previously fertilized by the father’s sperm.

An alternate procedure removes the donor egg’s DNA and replaces it with the parents’, she said.

This would result in an egg with mitochondria from the donor and DNA from the parents, she said. In total, the mitochondria encodes 37 genes in the new combined egg.

The mother and father each provide around 25,000 genes, Andrew Singson, a professor in the Waksman Institute of Microbiology.

Mitochondria are small parts of a cell that provide energy for cellular functions, Singson said in an email. Mutations in the mitochondrial DNA may cause diseases or disorders. By using properly-functioning mitochondria, diseases can be avoided.

This procedure will not work if the defects are found in the mitochondrial genes of the mother's cells, he said. The mitochondria have their own DNA, and this is what gets swapped in the procedure.

“Studies on humans suggest that about one in 10,000 people have some sort of mitochondrial disease and mothers can pass this disease through their eggs,” he said. “Of this, only about 15 percent are due to defects in mitochondrial DNA. The procedure can only benefit this tiny population.”

There are many disorders caused by mitochondrial mutations, said Jon Wilkins, an evolutionary biologist in the Department of Genetics. The mutations cause the mitochondria to lose functionality, which can cause muscle, neurological or metabolic problems.

These problems can range from diabetes to vision and hearing loss, to having trouble exerting oneself physically, he said. These conditions are presently difficult to treat.

“There are no therapies, there are no drugs and some of these disorders are quite severe,” Schindler said. “Those are the ones that they’re looking at, not the ones that are more compatible with life. The ones that they’re really pushing these technologies for are the most severe mitochondrial diseases.”

Children conceived through this procedure may be at a greater risk for other health issues, Singson said. Additionally, mothers may be at risk for complications with the assisted reproductive technology.

ART also may result in multiple births as multiple embryos are planted in the mother to ensure at least one becomes a child. Occasionally multiple children, such as with “Octomom," are birthed at the same time, he said.

In England, no more than three embryos may be implanted, while in the United States there are no limits, he said.

Some controversy exists over this procedure for religious and medical reasons, Wilkins said.

“You are messing with the DNA, which always makes people nervous,” he said. “Like all procedures involving manipulation of fertilized and unfertilized eggs, you are going to create some number of inviable, or viable but surplus, embryos, which bothers some people on religious grounds.”

The procedure itself carries some concerns, Schindler said. Manipulating embryos genetically has the potential to lead “down (a) slippery slope.”

Other uses for the procedure could help mothers with low quality eggs who have healthy DNA, she said.

Right now, the procedure will be done out of medical necessity, but in the future it could be used to select desirable traits in potential offspring, she said.

If the procedure is successful in the UK, it should be brought back to the US, Wilkins said. It was originally banned in response to its being used in the 90s.

The media has termed children born through mitochondrial (nuclear) transfer “three-parent babies” because they contain genetic material from three different people.

Considering the amount of genetic material donated by the third individual, this "third parent" would not have a significant legal claim, Singson said.

Defining “parent” is important to this discussion, Schindler said. Gametes are already donated at present for different procedures. The term “three-parent baby” has not been used to refer to children born from donated gametes even though they required three individuals.

“I feel like (the) term ("three-parent baby”), sure it’s marketing, but it may be a little misleading,” she said.


Nikhilesh De

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