First Human Embryos Edited in U.S.

[thejosh]

In a nutshell(i have to rush to classes) what i am implying is that genes often cross over during cell division, we call this mutation and it often happens in an organism to produce variation naturally, if we venture into introducing new genes (which is what we will eventually do) new mutations might occur which could potentially disrupt the path of nature, if and when this happens we could cause our own downfall rather than fix the issue, that is one of the main issues with impeding genetic engineering.I will post more later.

 

[Ygggdrasil]

what i am implying is that genes often cross over during cell division, we call this mutation and it often happens in an organism to produce variation naturally

Crossover events during cell division, which lead to a process known as recombination, is usually considered separately from the processes that create mutations. Recombination often helps the cell to repair mutations that occur when DNA is damaged during cell division. During normal cell division, recombination will usually not create genetic variation. Recombination that occurs during meiosis in the process of creating gametes leads to genetic variation by shuffling alleles between the two parental chromosomes, but usually does not introduce mutations.

 

[BillTre]

I can see how you might think of crossing over as being a mutation since it involves DNA breaks and changing the overall sequence, but as @Ygggdrasil, the term is not used that way.

At first I thought you were talking about two new mutations occurring at the same time which is highly unlikely since the probability of such a combination would be the probability of a mutation in one particular gene times the probability of a mutation in the other gene, which would be very improbably.

Synthetic lethals might be something like the idea you are trying to express.
They occur when two different alleles of two different genes come together in a single organism. This combination of alleles could be lethal (or just deleterious in less extreme cases) while the individual alleles themselves would not be.
These alleles could be either dominant or recessive in their synthetic effect (meaning you need only one or both copies of one of the alleles to be present to result in the synthetic effect).
The is an effect much like enhancers and suppressors have on other genes. Some enhancers can enhance the effects of another gene to the extent that it can cause lethality. These should not be confused with the enhancer sequences of molecular biology which thought to bind proteins and exist fairly near the gene they are affecting. Enhancer and suppressor mutations can be completely different genes.

If the two interacting genes are linked on a chromosome (they are physically linked by both being on the same piece DNA), they can not both be homozygous (both copies of a given gene the same) which is required for expression of recessive traits, unless recombination happens. After recombination, double homozygotes (or a homozygote and a heterozygotes would be possible for linked alleles, in the next generation.
There would be selection against this because lethality or other deleterious effects are non-adaptive.

This is independent of the source of the alleles involved (not particular to human generated genome changes) and can arise in hybrids or just from crossing between populations that have not had a lot of recent genetic interchange.
If new alleles were human introduced and they interacted with already existing genes to have bad effects, they would also be selected against, not just naturally, but also through human regulation since these effects (if significant) would be noticed and then researched. Certain gene constructs would be no longer made because they did not work well (regulatory agencies might get involved) and genetic consultation (which will develop along with the increased capacity to determine an individual's genome sequence) would advise against particular combinations (similar to what is being done already).

 

[Ygggdrasil]

Synthetic lethals might be something like the idea you are trying to express.
They occur when two different alleles of two different genes come together in a single organism. This combination of alleles could be lethal (or just deleterious in less extreme cases) while the individual alleles themselves would not be.
These alleles could be either dominant or recessive in their synthetic effect (meaning you need only one or both copies of one of the alleles to be present to result in the synthetic effect).

Synthetic lethality is a legitimate concern and one reason why guidelines recommend introducing only alleles that are already prevalent in the general population. That these alleles exist in healthy individuals with a wide range of genetic backgrounds ensures that these alleles would be unlikely to have unwanted synthetic genetic interactions with rare variants carried by some individuals in the population.

 

[Evanish]

Interesting thread. It gets into a lot of murky issues. I guess to sum it up I'd say the issue is who gets to choose the genetic makeup of unborn children. In the recent past the people that get to choose are the parents. They choose who they want to reproduce with. In the more distance past maybe the family would more often be the one who choses through arranged marriages. With this new technology maybe in the future other people/groups (governments, corporations, etc.) might in some way be more involved in this choice. Such powerful groups involvement will of course bring controversy as it bears some resemblance to the ideas of eugenics which many people have strong feeling about. I personally am in favor of the parents continuing to be the ones that make the final choice. Whatever genetic services that may be provided in the future they should be able to choose freely from among them with the minimal amount of pressure being applied to them by other people/groups (governments, corporations, etc.). As for what genetic services will be available that will surely be subject to regularity and financial constraints. Personally I think the regulations should be kept to the minimal as I think the individual parents have the right to choose for themselves what they thing is best for their unborn children.

 

[Ygggdrasil]

Researchers have raised doubts about the study by Mitalipov's team, suggesting that there could be alternative explanations for the authors' data. Stem cell biologist Paul Knoepfler describes the concerns on his blog:

An international team of top scientists led by first author Dieter Egli has responded via a preprint on Biorxiv to that Mitalipov team high-profile https://ipscell.com/2017/08/review-mitalipov-paper-Nature paper on CRISPR gene editing of human embryos. Egli, et al. raise the possibility that the CRISPR gene editing as reported in the Nature study may actually not have happened, at least not in every case and perhaps not the way the Ma, et al. paper argued it did (via homology directed repair (HDR)-based CRISPR-Cas9 action specifically depending on interaction between normal maternal and mutant paternal chromosomes).

On one level it isn’t so unusual to see a scientific critique of and technical questions raised about a published paper that made splashy news. However, I see this particular case as a striking turn of events because although the new Egli, et al. piece is very collegial and diplomatic, they convincingly lay out a number of rather compelling reasons why the main conclusions of the Ma paper might be incorrect and the reasons why there may not have been CRISPR gene editing in many of the embryos. To be clear, Egli and colleagues don’t seem to be saying the Ma, et al. paper is definitely wrong, but they describe some quite reasonable ways in which the Ma paper could hypothetically have inadvertently reached incorrect central conclusions. To me these possible alternative explanations just simply make a lot of sense and are things that should have been ruled out as alternative explanations.

https://ipscell.com/2017/08/doubts-...chnologies-wont-lead-designer-babies/']crispr-gene-editing-of-human-embryos/[/URL]

See also coverage at Science news: http://www.sciencemag.org/news/2017...chnologies-wont-lead-designer-babies/']crispr-human-embryo-editing-claims[/URL]

The critique of the study is available on bioRxiv: http://www.biorxiv.org/content/early/2017/08/28/181255

 

[stefan r]

Genetic engineering is a whole different ballgame. In fact, I don't really like the idea of genetic engineering on any animal species, much less humans. If you're going to experiment with it, keep it out of Kingdom Animalia.

Genetically engineered fungi could be scary too.

 

[lavinia]

Transgenic technology in mammals has existed for many years. Gene constructs originally were inserted into 1 cell embryos - in mice I think - and these constructs integrated into the genome and were expressed in the offspring.

A biologist told me that if one could insert genetic constructs into one cell human embryos then one could possibly cure various diseases. The example he gave was a cure for liver cancer. One would splice the promoter for alphafetal protein - a gene that is expressed in liver cancer cells but not in normal adult cells - with the gene for a Herpes protein that is fatal to the cell in the presence of a certain drug. If a liver cell becomes malignant then the promoter for alphafetal protein is turned on and the Herpes protein is produced in the cell. If one gives the drug, then the cell dies. Only the cancer cells will be killed and the normal cells will be unaffected. So in effect, liver cancer would be cured. Further this trait would be inherited.

The technological problem with this sort of therapy might be that the gene construct integrates somewhat randomly and might disrupt the genome - with unpredictable effects. If I understand it right, this current paper on CrispPR seems to say that this problem can be solved by restricting the genetic modification to a specific known site. This would remove the randomness and hopefully would not damage the chromosome. This might actually make genetic therapy feasible. It seems though that this is a technique that applies to single mutations and not multiple gene abnormalities.

 

[Ygggdrasil]

The technological problem with this sort of therapy might be that the gene construct integrates somewhat randomly and might disrupt the genome - with unpredictable effects. If I understand it right, this current paper on CrispPR seems to say that this problem can be solved by restricting the genetic modification to a specific known site. This would remove the randomness and hopefully would not damage the chromosome. This might actually make genetic therapy feasible. It seems though that this is a technique that applies to single mutations and not multiple gene abnormalities.

Correct. CRISPR shows promise in enabling scientists to make precise edits to the human genome. There is concern, however, that CRISPR could still make unintended, "off-target" mutations elsewhere in the genome and these off-target mutations have the potential to cause problems like cancer. More work needs to be done to assess the frequency of these off-target mutations and figure out how to minimize their occurrence. Still, when compared to other techniques that cause random integration of a transgene into the genome, CRISPR is a big step forward.

 

[stefan r]

...integrates somewhat randomly and might disrupt the genome - with unpredictable effects...

Does the meaning change if I quote just that part of a sentence? It looks like something a protester would say.

 

[lavinia]

In a nutshell(i have to rush to classes) what i am implying is that genes often cross over during cell division, we call this mutation and it often happens in an organism to produce variation naturally, if we venture into introducing new genes (which is what we will eventually do) new mutations might occur which could potentially disrupt the path of nature, if and when this happens we could cause our own downfall rather than fix the issue, that is one of the main issues with impeding genetic engineering.I will post more later.

Biologists that I know do not believe in a "path of Nature". Can you explain what you mean by this?

 

[jim mcnamara]

No. thejosh made several errors. There is no 'path of nature'. And single mutations alone will not wipe out a species - they are not a time bomb.
What I think he means is: If a mutation that is fatal homozygously (means just one allele of the the pair is required to have the effect) is common in a population, all people with it will die. But. How did it get into enough people long enough to be "common" in the first place.
Without killing them first?

What kills species is usually major environmental change, which usually occurs over periods longer than one lifetime. Sometimes a catastrophic event can cause a so-called population bottleneck (Founder Effect) . A few hundred individuals survive a major population die out. Modern cheetahs are an example of this.
See:

As a species, cheetahs have famously low levels of genetic variation. This can probably be attributed to a population bottleneck they experienced around 10,000 years ago, barely avoiding extinction at the end of the last ice age. However, the situation has worsened in modern times.

evolution.berkeley.edu/evolibrary/news/070701_cheetah