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Thread: gENOME RESEARCH.

  1. #1 gENOME RESEARCH. 
    Forum Ph.D. GhostofMaxwell's Avatar
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    How is genome research going lately, are we any nearer to altering our genes to cure cancer or extend our lifespam, for instance?


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    In short, no.


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    Most gene therapy ("altering our genes") is aimed at correcting faulty genes. There are candidate diseases for this sort of therapy, and such diseases typically need to meet certain criteria before becoming candidates for therapy.

    Most gene therapy uses a viral shuttle to transport the correct version of a gene into a tissue that will allow the gene to integrate and produce the required gene product. The main problem with this sort of therapy is that the viral DNA may insert in the 'wrong' place and cause problems (such as cancer.)

    This year's Nobel prizewinners in physiology and medicine, study gene targeting. Having genome sequence in hand facilitates gene targeting techniques. Gene targeting may be used in conjunction with ESC research, and embryonic stem cells may be able to replace viral methods of delivering a required gene to person who needs it.

    Genome data is also useful for the development of microarrays whjich are used extensively in early drug development at pharmaceutical companies.

    Evolutionarily, the genome data has elucidated that some of the changes between humans and chimps are down to numerous inversions in the respective DNAs, as opposed to sequence changes per se. DNA inversion may be a mechanism that facilitates speciation.
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    Forum Cosmic Wizard spuriousmonkey's Avatar
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    It is a bit of a tricky topic with no instant answers.

    The truth of the matter is probably that we still know very little, and most knowledge on transgenic models is generated in the mouse.

    The mouse is a good model system, but not a hyper-reliable representation of the human model.

    Most (all) of the knowledge on genetic disease on humans comes from disease studies. No experimental approach is possible. You simply cannot do experiments with humans.

    Which leaves us with the mouse and other model systems.

    The function of some genes is rather straightforward. The function of most genes is not. This has many reasons, and not all are known to us.

    An important factor is environment. The development of an organism is influenced by its external environment. The development of the brain is rather susceptible to environmental influences (toxins, infections, nutrition) which in itself is once again entirely dependent on genetic background. What is resulting in brain defects in one genetic background does not necessarily affect the brain development of other individuals.

    I hope that the reader of this post at this point already realizes what a quagmire this whole business is.

    Most of our knowledge is based on a rodent, a fly and a worm, we can't do experiments on the actual model system, each human individual is different, and we have no clue how everything is exactly interacting. And what is more, there is absolutely no way we can ever have the computer power to calculate all factors that are derived with reductionist research. The universe is simply too small to build a computer capable of it.

    Which means that we will be forced to use the black box approach with most genes to establish their function: trial and error.

    We know from the world of chemicals that things can go horribly wrong if you base your work on animal modes.

    Thalidomide was hailed as a wonderful drug able to relieve morning sickness, among other things. It was harmless in pregnant rats and mice.
    http://en.wikipedia.org/wiki/Thalido..._Birth_Defects

    But then children started to get born with serious birth defects. Mainly malformations of extremities.

    Turns out that human fetal development does not react that well to the drug as rodents did.

    And what is more, it is only a part of the fetuses that malform. Not all! And I must stress this point. Due to the genetic background, the external intervention had different effects.

    The same will be true for gene therapy interventions.

    There is no right human genome, no standard genome. We are all rather different, with a different collection of alleles of the same genes. And they interact. And we do not know exactly how they all interact and neither will we ever be able to exactly predict how they will interact.

    Many syndromes are linked to a gene. We have seen many reports in the media. That is, till you read the original paper in the peer-reviewed journal and discover that in many cases a large group of people has a mutation in the same gene, but a smaller group doesn't have a mutation here at all!

    The same defect can be caused by different agents, genetic and environmental, and what's more, they have a synergistic effect or a dampening effect.

    I will stop here. There is more to say on this topic, but this thread is still young.
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    Quote Originally Posted by spuriousmonkey

    There is no right human genome, no standard genome. We are all rather different, with a different collection of alleles of the same genes. And they interact. And we do not know exactly how they all interact and neither will we ever be able to exactly predict how they will interact.

    Many syndromes are linked to a gene. We have seen many reports in the media. That is, till you read the original paper in the peer-reviewed journal and discover that in many cases a large group of people has a mutation in the same gene, but a smaller group doesn't have a mutation here at all!

    The same defect can be caused by different agents, genetic and environmental, and what's more, they have a synergistic effect or a dampening effect.

    I will stop here. There is more to say on this topic, but this thread is still young.
    So what happened to all the optimism surrounding the human genome project?......We didn't get the new age in human genetics it was supposed to herald.
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    Quote Originally Posted by GhostofMaxwell
    So what happened to all the optimism surrounding the human genome project?......We didn't get the new age in human genetics it was supposed to herald.
    That optimism was mostly in the media and among certain groups of researchers.

    The current humane genome project in itself cannot guide genetic engineering.

    It's a very very very small step towards genetic enguneering.

    (imho)
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    Quote Originally Posted by spuriousmonkey
    Quote Originally Posted by GhostofMaxwell
    So what happened to all the optimism surrounding the human genome project?......We didn't get the new age in human genetics it was supposed to herald.
    That optimism was mostly in the media
    Yeah thats a point. Goddam circus freaks.
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    Certainly some sorts of experiments can be done on humans. Linkage studies (a type of experimentation) allowed the identification of BRCA as well as countless other disease genes. Many trials use human volunteers once a drug has cleared earlier trials in animals.

    Gene therapy trials ask for volunteers, and have had some stunning success (along with stunning failures). See XSCID.

    Genome sequencing is now so rapid, that it can be accomplished for simple organisms in a matter of weeks. Our lab recently sent out an isolate from the environment that is involved in methane consumption, and the returned genome data gives unexpected insight into this organisms additional metabolic capabilities. Several online websites allow public access to the many (dozens or hundreds) genomes that are currently completed.

    Neandertal DNA is presently being sequenced. This will shed insight into recent human evolution.

    Regarding cancer (as per the OP): Drug companies rely on microarrays to analyse gene expression following various therapies. Lance Armstrong's drug Epogen, for example, was developed with microarray data. Microarrays rely on genome data - and proteome data.

    I don't disagree with anything that has been said except the sentiment that genomics has not delivered. It has not delivered instant gene-fixes at the local shop, perhaps, but genomics are indispensable in many areas of scientific research.
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    even though the human genome project was portrayed to the public as being complete, we are still far way from knowing what every thing dose.

    no is the answer, but yes its moving along.
    Stumble on through life.
    Feel free to correct any false information, which unknown to me, may be included in my posts. (also - let this be a disclaimer)
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  11. #10  
    Forum Cosmic Wizard spuriousmonkey's Avatar
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    Of course recently the first diploid human genome sequence was pubished.

    http://biology.plosjournals.org/perl...l.pbio.0050254

    A new 'major' step on the way of genome sequencing.

    Diploid means that we have two copies of each chromosome. One of the mother and one of the father. Obviously they are not the same, so this project was started to see the differences.

    I find them a bit too optimistic though.

    First and foremost, as we show in a preliminary analysis, genome-based correlations to phenotype can be performed. Due to the still rudimentary state of the genotype-phenotype databases it can be argued that at the present time, DNA sequence comparisons do not reveal much more information than a proper family history. Even when a disease, predisposition, or phenotypically-relevant allele is found, further familial sampling will usually be required to determine the relevance. Eventually, however, populations of genomes will be sequenced, and at some point, a critical mass will dramatically change the value of any individual initiative providing the potential for proactive rather than reactive personal health care.
    They still hold on to the old thinking that the genome is a blueprint.
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  12. #11  
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    Quote Originally Posted by spuriousmonkey
    They still hold on to the old thinking that the genome is a blueprint.
    Just to be clear, you mean in contrast to the more accurate recipe analogy.
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