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CONTENTS, ENGLISH, General, GENETICS

Abrahim’ story: the child with 3 people’s DNA

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On last 27th September media echoed with the news of the first birth of a child with DNA from three people, through the experimental technique, called spindle nuclear transfer. What is this technique? Is it possible to have DNA from other people besides our parents? Then, I will explain the news in detail.

THE FAMILY

We need to know well his parents. They are a couple from Jordan, whose wife is a 36-year-old woman with a gene mutation in her mitochondrial DNA. It is right: mitochondrial DNA. A part of the nuclear DNA, where is found in our cell’s core and we currently mean, there is also DNA in our mitochondria. Mitochondria are double membrane-bound organelles found in all eukaryotic organisms and play a crucial role in energy production. They are necessary for our cells breathe and produce energy.

Like nuclear DNA, mitochondrial DNA can suffer mutations caused inherited diseases. For example Leber’s hereditary optic neuropathy (LHON), a rare inherited disease that causes blindness due to degeneration of the optic nerve.

Well, the mutation suffered by the protagonist of the story in their mitochondrial DNA cause Leigh syndrome. It is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. Clinical symptoms depend on which areas of the central nervous system are involved.

Mitochondria are inherited only from mothers, a pattern known as maternal inheritance. This is the reason that they need to find a solution and avoid to transmit mitochondrial DNA (with mutations) to offspring. Previously, she had 4 pregnancy losses and 2 deceased children at age 8 months and 6 years from Leigh syndrome. The percentage of mutant DNA in mother’s mitochondria is enough for her to have no symptoms of the disease and only be a carrier. However, the probability of transmitting the mutation to offspring is very high.

THE TECHNIQUE: SPINDLE NUCLEAR TRANSFER

The couple sought out the help of John Zhang and his team at the New Hope Fertility Center in New York City. They work researching techniques to prevent diseases caused by mutations in mitochondrial DNA.

Currently, there are two methods for mitochondrial replacement: pronuclear transfer or transfer of the mitotic spindle. In both cases a donor is needed, who has not any mitochondrial DNA mutation.

The first technique is called pronuclear transfer (Figure 1) and involves fertilising both the mother’s egg and a donor egg with the father’s sperm. Before the fertilised eggs start dividing into early-stage embryos, each nucleus is removed. The nucleus from the donor’s fertilised egg is discarded and replaced by that from the mother’s fertilised egg.

But this technique wasn’t appropriate for the couple for religious reasons (they are Muslims). And this method involves the destruction of two embryos.

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Figure 1. Pronuclear transfer. An egg from the mother (yellow) and an egg from the donor (purple) are fertilized with sperm from the father (yellow). When the pronucleus is formed in each egg, its is eliminated from the donor and the mother’s pronucleus is inserted in the donor’s egg (Source: A Scientist’s Guide to Making Babies…)

So Zhang’s team took a different approach, called spindle nuclear transfer (Figure 2). They removed the nucleus from one of the mother’s eggs and inserted it into a donor egg that had had its own nucleus removed. The resulting egg (with nuclear DNA from the mother and mitochondrial DNA from a donor) was then fertilised with the father’s sperm.

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Figure 2. Spindle muclear transfer. The red egg corresponds to the mother, and her mitotic spindle is removed and inserted into the donor’s egg (orange), which previously has been extracted her mitotic spindle. Later, the egg is fertilized with sperm from the father (blue) (Source: Revista Genética Médica, modification)

In either methods the new egg is 100% free of maternal mitochondrial DNA (mitochondrial DNA with mutations) because it is estimated that about 1% of the mitochondrial DNA can be entrained with the nuclear genetic material. However, it is considered that the levels are low enough to cause Leigh syndrome.

THE CRITICS

The procedure is not legal in the United States, so it was done in Mexico, where rules around human embryo manipulation are more lax than in the United States, which has declined to greenlight the experimental procedure.

The technique has gained notoriety because it leaves the baby with three genetic parents. But there is a part of the scientific community that is not quite agree because he fears are not complied with all ethical codes. The limited information in the abstract left many wanting more.

Zhang’s team created 5 embryos and only one had a normal karyotype (46,XY). It was implanted into the mother and 9 months later Abrahim was born (Figure 3). He is a boy and there is no risk to transmit his mitochondria (donor’s mitochondria) to his offspring.

Now, this Jordanian family enjoys their healthy baby at home, and for the moment the mutation was detected in less than 1% of mitochondria

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Figure 3. Fertility specialist John Zhang with the newborn baby Abrahim (Source: Science)

REFERENCES

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