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Location of defective gene assisting in future treatments

Genetics as it applies to evolution, molecular biology, and medical aspects.

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Location of defective gene assisting in future treatments

Postby sableg » Wed Dec 09, 2009 8:52 pm

So the exact question is "How can knowing the location of a defective gene assist in developing future products or treatments for that gene?"

I've done some research on gene therapy and I'm thinking I should base my answer around using viruses to insert genes into cells that are needed. I understand that this process involves altering a virus by removing the disease carrying genes and replacing it with the desired effect. This would mean that if you were trying to treat diabetes you would put in insulin producing genes into the virus for the desired effect. However I'm getting off topic and struggling to link this back to "knowing the location of a defective gene" and developing FUTURE treatments and products. I just can't seem to find the link between finding the location of a defective gene and developing future treatments and products.

Here is an answer that I was thinking of but doesn't seem quite right because I can't PROPERLY tie in the LOCATION of the defective gene.

Knowing the location of a defective gene can assist in developing future products and treatments for that gene. The first step to treating a defective gene would be knowing its location so you could use gene therapy as treatment. A form of gene therapy is vectors this involves altering a viruses genetic material so it inserts DNA with the desired effect for the cells rather than the original disease or it would usually insert. It is important to know the location of the defective gene so you can effectively treat it with vectors because if the location of the defective gene is unknown you would not know what genes to put into the virus to produce the desired effect. For example, to treat diabetes in the future we could use this type of gene therapy by inserting genes into the virus that produce insulin then exposing the body to this virus so it encodes this information into the cells. First you have to know the location of the defective gene to know what type of gene to put into the virus.

All help greatly appreciated! :)
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Postby mith » Thu Dec 10, 2009 3:39 am

I don't think a vector knows where it will splice into.
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Re:

Postby sableg » Thu Dec 10, 2009 4:24 am

mith wrote:I don't think a vector knows where it will splice into.


That is what I was thinking. I can't think of how knowing the location will do any good in developing future products or technology. There would have to be something totally new dreamed up. Something that could just repair that specific gene but genes are so small you couldn't just replace the gene. Vectors replace the whole DNA. It makes no sense :shock:
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Postby Eous » Thu Dec 10, 2009 8:38 am

The concept of using a virus like you propose works in princible, but is much more complicated in practice. A construct can be made to be inserted into the genome just like the viral DNA would be. Normally, viruses are not specific in their insertion placement, meaning if you tossed insulin producing genes (with the appropriate flanking sequences) into a virus and tossed that virus into a clump of receptive cells, you would probably end up with at least a couple cells that got the gene incorporated into the genome, and perhaps a small percentage of those might actually start producing insulin, and that's without attempting to specify where the genes incorporate (and that's also a lot simpler than it actually has to be). If you tried to aim the insertion, using some sort of sequence speceficity, you would have extremely little success, and you would most likely also get insertions in other places. And this success would require loading a large amount of virus into the cells, or making a virus that will reproduce itself throughout the system and also carry the genes you want to distribute. (and in terms of a system, it will be outstandingly difficult to control this in a large eukaryote; you might be able to pull it off in a nematode, maybe, but this is why i'm talking about just putting it into cells in a dish or flask or something) but whenever you're dealing with a virus, you chance it evolving, which they tend to do rapidly, so it might become dangerous of its own accord, and then you have a wolf problem. there's also the chance that the insertion will be in an unfortunate enough place in the genome as to cause cancer. But regardless, in terms of higher eukaryotes, currently, this concept is not a viable option, especially if you need to target a region of the genome, and if you're not, it doesn't answer your question.

Now, to actually help answer the question; the location of a defective gene in a genome can be completely useless information, or it can be of utmost importance. It depends primarily on why the gene is defective. Say a gene that is normally constantly transcribed throughout the body has a major deletion and so is no longer viable. If you just want the gene to be there in working form, it doesn't matter where it is even if you have a way to put a gene into the geneome (maybe). There are many instances where placement entirely matters. The location of genes usually results in specific regulation patterns. I don't want to get too much into epigenetics, but suppose that those insulin producing genes are regulated locally by site specific interactions with another gene. Putting the insulin producing genes just anywhere won't keep them under the same regulation so they won't work appropriately unless they're in the correct region to be transcribed in the right place in the body. in this case, it would help to know the location of those genes in the genome to know what kind of treatment is important - can you just put a gene anywhere, or do you have to try and aim it - again, if you do have to aim it, you're better off just supplying the body with whatever that gene would produce. But perhaps the mutation isn't in the exact gene that you see failing, maybe its in the site that is used for regulating the whole genomic region, maybe its in one of the transcription factors used to regulate the region, whos gene is perhaps locate an chromosome away. If you can detect which genes are defective, it's important to know where they are to know how they are regulated. Because, it would be best to give someone the exact thing they need. I could give someone all the insulin they need, but maybe the entire genomic region is failing and they have some other problem i haven't notice and will not if i cure them symptom by symptom. So yeah, knowing the location of a gene can tell you a lot about the regulation of it, which can lead to the more appropriate treatments of the defect. a large portion of cancers occur because genes accidentally move to regions that are under a different regulatory scheme, causing an increase or decrease in transcription.

I could go on, but i think that should be enough to give you a sufficient start on fully answering that question. If it's not enough, just ask more questions.

(all of this has been completely speculative, as i don't know much about the specific regulation of the insulin genes, and i'm no virologist, but again, the princibles are fairly sound)
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Re:

Postby sableg » Thu Dec 10, 2009 1:33 pm

Eous wrote:The concept of using a virus like you propose works in princible, but is much more complicated in practice. A construct can be made to be inserted into the genome just like the viral DNA would be. Normally, viruses are not specific in their insertion placement, meaning if you tossed insulin producing genes (with the appropriate flanking sequences) into a virus and tossed that virus into a clump of receptive cells, you would probably end up with at least a couple cells that got the gene incorporated into the genome, and perhaps a small percentage of those might actually start producing insulin, and that's without attempting to specify where the genes incorporate (and that's also a lot simpler than it actually has to be). If you tried to aim the insertion, using some sort of sequence speceficity, you would have extremely little success, and you would most likely also get insertions in other places. And this success would require loading a large amount of virus into the cells, or making a virus that will reproduce itself throughout the system and also carry the genes you want to distribute. (and in terms of a system, it will be outstandingly difficult to control this in a large eukaryote; you might be able to pull it off in a nematode, maybe, but this is why i'm talking about just putting it into cells in a dish or flask or something) but whenever you're dealing with a virus, you chance it evolving, which they tend to do rapidly, so it might become dangerous of its own accord, and then you have a wolf problem. there's also the chance that the insertion will be in an unfortunate enough place in the genome as to cause cancer. But regardless, in terms of higher eukaryotes, currently, this concept is not a viable option, especially if you need to target a region of the genome, and if you're not, it doesn't answer your question.

Now, to actually help answer the question; the location of a defective gene in a genome can be completely useless information, or it can be of utmost importance. It depends primarily on why the gene is defective. Say a gene that is normally constantly transcribed throughout the body has a major deletion and so is no longer viable. If you just want the gene to be there in working form, it doesn't matter where it is even if you have a way to put a gene into the geneome (maybe). There are many instances where placement entirely matters. The location of genes usually results in specific regulation patterns. I don't want to get too much into epigenetics, but suppose that those insulin producing genes are regulated locally by site specific interactions with another gene. Putting the insulin producing genes just anywhere won't keep them under the same regulation so they won't work appropriately unless they're in the correct region to be transcribed in the right place in the body. in this case, it would help to know the location of those genes in the genome to know what kind of treatment is important - can you just put a gene anywhere, or do you have to try and aim it - again, if you do have to aim it, you're better off just supplying the body with whatever that gene would produce. But perhaps the mutation isn't in the exact gene that you see failing, maybe its in the site that is used for regulating the whole genomic region, maybe its in one of the transcription factors used to regulate the region, whos gene is perhaps locate an chromosome away. If you can detect which genes are defective, it's important to know where they are to know how they are regulated. Because, it would be best to give someone the exact thing they need. I could give someone all the insulin they need, but maybe the entire genomic region is failing and they have some other problem i haven't notice and will not if i cure them symptom by symptom. So yeah, knowing the location of a gene can tell you a lot about the regulation of it, which can lead to the more appropriate treatments of the defect. a large portion of cancers occur because genes accidentally move to regions that are under a different regulatory scheme, causing an increase or decrease in transcription.

I could go on, but i think that should be enough to give you a sufficient start on fully answering that question. If it's not enough, just ask more questions.

(all of this has been completely speculative, as i don't know much about the specific regulation of the insulin genes, and i'm no virologist, but again, the princibles are fairly sound)


Thank-you!!! This was incredibly helpful and has given me a turbo boost on answering my question. This question is for grade 11 biology and all we covered on genetics so far is the difference between genes, chromosomes, DNA and RNA that is why I was struggling on where to look for an intelligent answer with such minimal background information.

I hate to pick your brain but... As far as the development of future products and treatments for the gene is concerned would knowing the location of the defective genes (this is where it gets a little sci-fi because this is grade 11 biology and I think they just want us thinking outside the box within some realm of intelligence) assist in developing future products and treatments that could perhaps directly insert the correct gene into the DNA at the appropriate site of the body (this would involve very small tools and IMHOP would be impossible), or would a vector be a viable answer for my work because at my level I'm not expected to know all the complications so I could write about how in the "future" :lol: vectors could be engineered specific enough to target the exact location of the body where the defective genes are (whether it be where the insulin is produced or where it is transcribed that is where knowing the location of the defective gene would com in handy). Thanks again :D
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Postby Eous » Thu Dec 10, 2009 7:26 pm

You are correct to think that it would be slightly entering the realm of science fiction, but then again, most science fiction is presumably reprensentational of a possible future. With enough knowledge of all of the factors making up the path a DNA altering vector, such as a virus or microorganism(using vector in the broader sense for a moment) would have to take, it would certainly be possible to construct a reliable mode of tissue specific and site specific DNA alteration. The knowledge would have to be extraordinary, and by that time i feel that a number of other safer, easier solutions would have been reached by biotechnology or what-have-you. With infinite knowledge of biological systems on all levels, and the ability to construct whatever is needed (whether by making things from scratch, or manipulating existing vectors), almost everything your grade 11 biology class could fathom would be possilbe. There are many microorganisms and some higher eukaryotes that are amazingly good at efficiently targeting, the underlying mechanisms of which have yet to be understood.

The only problem I see with the arguement is the supposition that this is where the science is headed. And while it could head the way of more and more specificity in constructed molecular targeting, it seems to me that it is content to avoid as much microscopic speculation as possible. Instead of supplying a vector to fix a persons DNA, which has to do all the targetting itself, health care professionals would simply replace whole populations of cells or tissues. Perhaps they might surgically take a persons cells (true stem, or induced pluripotent), fix any problems they suppose in vitro (maybe replacing the entire genome with a proper one), and then surgically put them back. Something like that would initially require knowledge of gene loci for development of individual treatments, but then could be reproduced by people without such knowledge. But again, gene location would important mostly because of differential genetic regulatory elements. And while that approach is not as deep in science fiction, it still involves a bit.

Hope that helps. :)
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Postby mith » Fri Dec 11, 2009 2:02 am

I think in a more present day answer you could say something along the lines of, if you see an abnormality in chromosome Y and you know gene X is on Y, then you could make some predictions for family planning etc
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