There are many problems with this article that are equally worth - TopicsExpress


There are many problems with this article that are equally worth addressing and I will not have time to discuss them all here. I do, however, want to mention that there is almost complete lack of addressing the mitochondrial disease experience. There is only one patient story (a video) where a woman describes having an X-liked disorder that has effected her mitochondria. Her chance of having a kid with the disease is 50% . It is unclear whether her disorder also involved mutations in her mitochondria (mtDNA mutations) that required the use of pronuclear transfer. It appeared that only standard IVF procedures, like the ones in America, were used to determine whether the allele she inherited from her dads X chromosome was present. In that case, it is irrelevant to the argument as to why pronuclear transfer is necessary. Most importantly, it does not address the symptoms commonly seen in children with mitochondrial disease (deafness, blindness, metal retardation, stoke, and death). Im going to leave this problem and focus on the ones that I see happening more often with this topic, misinformation and misnomer. Names like “genetically modified babies” imply that there is genetic modification being done. There is no genetic modification being performed in pronuclear transfer. There are no genes being inserted or deleted. The mitochondria are inherited in the way that they are normally inherited: A group of mitochondria are provided to the cell. The mitochondrial DNA are contained in the mitochondria. Nuclear DNA is contained in the nucleus. I also think that the procedure is generally done with the nucleus being removed and transferred, not the mitochondria. So their graph explaining the procedure is wrong. Terms like three-parent babies and three-parent IVF are also wrong. A genetic parent is a parent who conceives a child. Mitochondria are not used in fertilization (e.g., eggs cannot be fertilized with mitochondria and sperm cannot be used to fertilize mitochondria). More specifically, mitochondrial DNA (mtDNA) is not involved in the “fusion” of parental DNA that happens in the nucleus during fertilization. In fact, mitochondria from the sperm are completely cast away with the tail when the sperm head is absorbed in the egg. If the presence of mitochondrial DNA was used as the definition of a genetic parent, our fathers would not be our parents. Our fathers are of course our parents and this is because we use nuclear DNA to establish a genetic parent, not mitochondrial DNA (or lack there of). You may argue that because genetic fathers do not contribute mitochondria, we dont use it in our definition of a genetic parent for them, but we can still use it in our definition of female genetic parents. There are several ways that I can attack this, but Ill restrict it to one... and it happens to be the most important part of my argument, so listen up close. You cannot call someone a genetic parent strictly on the basis of “the presence of genetic material”. With that basis, anyone that kisses your mother and gives her a virus where the retroviral DNA inserts itself into her eggs before you were born, would be considered your genetic parent. Can you imagine someone saying, “I’m pretty sure Bill Clinton coughed on my mom before she was pregnant with me. Time for a paternity test!” How can we take that argument seriously? Even if it could somehow be determined that without a doubt part of your nuclear DNA was derived from the viruses that are now dormant in his DNA, this would NOT establish him as a genetic parent. The fact is that endogenous retroviruses make up anywhere from 3-8% of your genome. Compare that to the less than 5 ten thousandths of a percent of DNA that a mitochondrial genome would take up if you inserted it into your nuclear genome. But there is really no point in making this comparison at all because mitochondria do not inject their DNA into the nucleus. Sperm, viruses, and other parasites do. You might want to argue that the presence of so many mitochondria in the egg must account for something. My response to this argument is, it doesnt make sense to use the 100,000 mitochondria in an egg in our discussion of genetic relation because 1) there are less (sometimes zero) mitochondria present in the various cells of the body after the egg divides and 2) you are trying to equate the number of mitochondria to the genetic contribution of mitochondria and they are not the same thing. The differences between mtDNA in mitochondria are like the differences you have in the nuclear DNA between cells. When we talk about a nuclear genome we are talking about the genes in a single nucleus. When we talk about a mitochondrial genome, we are talking about a circular chromosome in a single mitochondrion. DNA length and quantity can not be used as indicators of functional contribution to the cell. For that we would have to look at whether mitochondria were actually making ATP and how much was being made (i.e., whether their genes are actually working and how often they were turned on). To determine the functional contribution provided from nuclear DNA would be even more complicated. We know that 93% of DNA is noncoding, but that doesnt tell us how often the genes are expressed (if at all). The problem is that genes are turned on and off at various times throughout our lives and there is no way to determine when and if that will happen because it is largely a product of our environment. For example women have all the genes necessary to make a penis, but they arent turned on because it requires the presence of a specific amount of testosterone in utero. Arguments for establishing a genetic parent based on genetic contribution lead us no where because its not something you can effectively measure. If we neglected function entirely, and we neglected nuclear composition (the X chromosome is much bigger than the Y chromosome), and included all the mtDNA in the hundred thousand mitochondria present in the egg, what we would effectively be saying is this: each of us is two thirds related to our mother and only one third related to our father. We never say this… and for good reason. The effects of mitochondrial DNA are limited to what mitochondria do: make ATP. The characteristics that we think of when we talk about inheritance (e.g., your mothers wit and your grandmas eye color) are not the kinds things you can inherit through mitochondria. All that can inherit from donor-mitochondria are functional mitochondria. Instead, we say that a human is 50% related to their mother and 50% related to their father. When we say this, we are talking about nuclear DNA. We will see this exact same ratio (50/50) in children whether their parents use IVF assisted technologies or not. We could also be talking about both (nuclear genome + mitochondrial genome) but no matter how you look at it (size, function, mode of inheritance, etc.) the contribution of mitochondria is so small compared to the nuclear genome that to look at both of them the same time is the same as only looking at the nuclear genome alone. ATP is a chemical like oxygen, is very important and every cell needs it to survive. But not all of the credit for making ATP can be attributed to mitochondrial DNA. Mitochondria do not posses many of the genes required for making ATP and they rely on the presence of these genes in the nucleus. The nuclear genes make these proteins and deliver them the mitochondria. Our cells can also make ATP without mitochondria (glycolysis) but the mitochondria do it better. The process of IVF described in the article is called pronuclear transfer. Babies born from parents using IVF assistance (with or without pronuclear transfer) are simply called “babies”. Feel free to use terms like “three-parent” and “genetically modified” when they actually describe something. To use them here is wrong (in both the linguistic and the moral sense). Using terms inappropriately in order to generate fear is morally wrong when it causes human suffering. The fear prevents a valid treatment (and the only known prevention of mitochondrial disease) from ever being used.
Posted on: Sat, 17 Jan 2015 00:11:02 +0000

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