Tuesday, 18 August 2015

Britain: three parents to make a baby

To prevent transmission of a genetic mutation from the mother responsible for a severe disease, Britain does allow a human embryo to be genetically modified? Specifically, it follows from the meeting of three DNA, her mother, her father and another woman? Or to put it more simply, a baby can have three biological parents?
This method of medically assisted procreation for preventive has been advocated Tuesday, June 3 by the British regulator of reproductive methods, the Human Fertilisation and Embryology Authority (HFEA), which had been requested on this sensitive issue by the Ministry of health. This is to avoid that the child inherits from his mother carried a mutation on the mitochondrial genome.

Mitochondria are oval structures present in the cytoplasm of cells. They play a central role in cellular energy metabolism. But one of the peculiarities of these subunits, genuine energy plants, is to possess their own genome, called mitochondrial DNA, which is exclusively maternal transmission. Mitochondrial DNA (mtDNA) thus differs in location of said nuclear DNA, that contained in the cell nucleus. Genes in mtDNA are dedicated to the production of a very important constituent enzyme system proteins "respiratory chain".
Mitochondrial diseases are the most common inherited metabolic diseases. They are due to a dysfunction of the mitochondrial respiratory chain. The presentation of these severe diseases without cure to date, is very heterogeneous. Indeed, they are reflected as appropriate by a neurological disease (particularly by complex syndromes or combined), neuromuscular (mitochondrial myopathy infant lethal), deafness and epilepsy, ophthalmologic disease causing sudden loss of vision ( Leber hereditary optic neuropathy), heart (hypertrophic heart disease), kidney. Some of these diseases, often involving several organs, are potentially fatal during childhood. One mutation in the other, the spectrum of disease is extremely variable.
The technique, developed at the University of Newcastle, involves removing the nucleus of a cell (from a woman carrying a mitochondrial mutation) to transfer into a cell of a healthy woman whose nucleus has been removed . The donor cell then contains over its nuclear DNA, replaced by that of the mother, but maintains its own mitochondrial DNA. This oocyte handled thus has two DNA (nuclear and mitochondrial) from two women (mother and oocyte donor). After fertilization by the sperm of the father, the result is an embryo that contains three DNA from two women and one man.
In total, the baby resulting from such manipulation will contain the DNA of three people: his father and mother which is the nuclear DNA but also of another woman of her donor mitochondrial DNA. The latter will be transmitted to future generations when the child, as an adult, will have the reproductive age.
Two techniques known as "nuclear transfer" may be used depending on the stage of development of the cell in which the nucleus is removed: a mature egg or a fertilized embryo at the stage of egg cell (or zygote).
The report of the British Authority on the Human Fertilisation and Embryology (HFEA) concluded that this method of in vitro fertilization three parents "does not appear not to be safe" [not unsafe] and is "potentially useful "for a specific group of women. The panel of British experts added that the available data do not yet allow to favor one of the two techniques of nuclear transfer and above all other experiences, including on human embryos in the laboratory, will be needed.
This is the third time that the HFEA experts are in favor of this approach. If used, Britain would appear in leading global IVF in the prevention of the transmission of mitochondrial diseases. This panel had issued a positive opinion on this issue in 2011 and 2013.
The British government hopes that new legislation will be adopted in the Parliament by the end of the year that will allow IVF three DNA. A technique that could be used within two years for women whose family genetic history would show a significant risk of transmitting a particularly severe mitochondrial disease. Identifying patients likely to benefit from this technique will require the participation of reproductive biologists but also genetic counseling experts in mitochondrial diseases, a very different context from that of all other communicable diseases by genetic DNA mutation Nuclear.
Each year, ten women (conducting a mutation in mitochondrial DNA, but not necessarily sick) could be used in Britain to this method of nuclear transfer.
This technique of genetic modification of the oocyte or embryo, which is similar to that of cloning (which also replaces the nucleus of a cell by another), is not without asking for obvious ethical issues, but also scientists. Indeed, as I detailed in Dr. Jean-Paul Bonnefont, researcher at Inserm (Necker Children's Hospital, Paris), it is not impossible that the triple parental origin of DNA can affect the interaction between core and mitochondria. In other words, the question arises whether the introduction of a mitochondrial DNA from a different woman than the one which comes from nuclear DNA may disturb the dialogue between mitochondria and nucleus. With what potential long-term consequences?
In the US, the Food and Drug Administration (FDA) is also considering the possibility of using this procedure for preventive micromanipulation. She recently concluded that "there is probably not enough data both in animals and in vitro to engage in clinical trials." It is important in her first derésoudre other questions about animal testing (significant percentage of embryo implantation loss micromanipulated by default, in particular) and other relevant basic research.
Today, in France, a diagnostic method usually performed preimplantation embryo conceived in vitro to stage 8-cell blastomere (3 days after fertilization) exists for early detection of mitochondrial diseases and implant the embryos do with no mutation or posing only a low rate (below 30%) of mtDNA molecules mutation carriers compared to the entire mitochondrial DNA. However, in cases where the mutation is present in all copies of mtDNA, women have not only recourse for oocyte donation.
In Britain, children born through nuclear transfer technique will not be allowed to know the identity of their "third parent", ie their "second mother".
That day, probably will do you speak of children from genetically reconstituted families, one of the two mothers remain forever anonymous. Nuclear or mitochondrial DNA, which will have more room in parenting in this particular genetic background?

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