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The genome project - success or failure?

The instructions for life, it turns out, are an intriguing and complex list of many parts.

DNA - Illustration, by Michael Struck, Wikipedia
DNA - Illustration, by Michael Struck, Wikipedia

When the scientists finished sequencing the human genome, the world expected the solution to all the diseases in its wake. Six years after its completion, expectations are taking a much more realistic turn. Genetics is just not that helpful in predicting who will get sick and why. The instructions for life, it turns out, are an intriguing and complex list of many parts.

בAn article published this week In the prestigious magazine Nature, the researchers discussed different approaches to finding the missing heritability of the genome, with an emphasis on complex diseases. Yes, it turns out that it is much, much more complicated than what was explained to us in the XNUMXth grade.

Reminder: the hereditary material, DNA, is made up of a ladder made up of four types of molecules named A, C, G, T. The way the letters are arranged determines the way the genetic code is translated, leading to the creation of proteins. The proteins in turn build the body. There are differences in the order of the letters between humans, this is the reason why we do not look exactly the same, why some have light hair and others dark, and also why some of us are sick and others are not.

The method used until now to find genetic differences that explain the appearance of one disease or another, was to compare such letter sequences from thousands of people, sick and healthy, in the hope of finding a significant difference. But this method did not lead to many results. True, there are diseases that can be explained, such as sickle cell anemia, but most of them cannot be explained.

For example, in one of the recent studies conducted with the aim of finding a genetic basis for schizophrenia, after a review of 50,000 people, they found 10,000 differences, each of which increases the chance of the disease by only 0.2%, and all of them together explain only 30% of the chance of developing the disease. The other 70 percent comes from other, environmental factors.

What is meant by "missing heredity", what is missing there? Genetic variation may lead to a 2-3-fold and even 30-fold increase in the risk of the disease, but in practice, when you look at the sick people and their families, you find only a 50% increase in the risk of developing the disease. Are the numbers a bit confusing? Here is a slightly simpler example: suppose they found that a person with a certain genetic variation has a double chance of developing a disease, but the hereditary risk is one in a hundred, in fact we linked only 2 percent of heredity to genetics. This gap is the missing heredity, meaning that there is something else besides the DNA sequence that plays a role. The gap varies, in some diseases there is a description of about half of the genetic inheritance. But this is the exception, in most diseases the link is only about five percent.

There are many thoughts about the relationship between DNA and the environment, if you are not exposed to a variety of environmental factors, you may never develop a certain disease. Conversely, with enough bad environmental exposure you may get a disease regardless of your genetics (skin cancer for example).

Several reasons have been put forward that could explain some of the missing heritability. Among them, differences inThe number of copies of each gene, or the way genes are activated (epigenetics) by methylations. Genes are activated in different places in the body differently, genes related to vision have no use in the legs for example, but the amount of activation of a gene in the eyes that varies between species can affect different vision abilities. also The physical manner in which the genes are distributed in the genome (say on the same chromosome or on different chromosomes, close to each other or far apart in terms of the three-dimensional folding of the genome). The answer to the riddle is probably, all the answers are correct.

So genomics is worth nothing anymore? It must be worth it, it's just much more complicated than thought so far. The hope was that once we identified where everything was, and had the exact sequence, and all the differences that could be in the garden, it would explain everything. Hopes apart and reality apart.
Since it is still not possible to explain a significant part of the hereditary tendencies between people, it seems that the information that can be obtained from the private genomics companies is not particularly useful in predicting the development of certain diseases in the future. There are probably many other factors that increase the risk of many diseases, and these can be explained better than genetics. For example, the connection between poor nutrition and heart attacks. Genomics, meanwhile, is mainly a research tool without too many practical implications.

The tools for cracking the heredity puzzle exist, the cost of paving is decreasing and it is becoming more reliable, but the method of deciphering is becoming difficult. The technologies for decoding continue to develop and there will be technological requirements that will be discovered in the future. It is very difficult to give a time forecast. It turns out that the gap between science and science fiction, at least in the field of genetics, is greater than it first seemed. In the coming years, many more differences will be discovered, and some of them we can even explain, but most of them not. In general, it is useful to think of genomics as a series of clues, instead of looking for absolute answers.

9 תגובות

  1. So like in the joke about the sailor who tells the captain that they sunk a submarine, then the captain asks the sailor if he is safe? Did you see bubbles, oil stains or fractures? When the sailor says no, the captain dismisses him with contempt. So the sailor says ok, but what will we do with all the prisoners?
    So here, too, what do we do with the diseases after the human being has broken down and fallen ill? Because we didn't find it in the gardens, so we will solve it as something that has no solution?
    After all, it will be more difficult to send the same mentally ill or diabetic patient to live a whole life again in the hope that this time the environment will not lead to the expression of the genetic disease.

  2. light
    Good night
    Your words are acceptable, but we require an improvement in our observation of development. Even if we assume that the cost of maintaining excess DNA is not high [an assumption that is difficult for me to accept - any increase in the system increases the chance of mistakes and when] after all, the abstract definition you gave "uselessness to the organism but Still useful to himself" an interpretation of cost/benefit must be given. The result is that we will have to interpret as if the mechanism preserves future options for itself at the expense of efficiency. It is difficult to accept such assumptions because they require recognition of the parameter of 'aspiration' or 'awareness' or 'will'. Instead of these I simply assume that those sections have a role in the control procedures at least. It is also likely that they have a part in conditioning procedures. I mean under what conditions [both timing and environmental feedback] will the specific gene be expressed.

  3. Joel,

    It is important to remember that the "goal" of nature is not to create organisms that are beneficial to themselves, but genes that are beneficial to themselves to reproduce and survive. The reason the "junk DNA" idea caught on is that the same DNA may be useless to the organism, but it is still useful to itself - and that is what determines its survival. Since the cost to the organism of holding unnecessary DNA is not high, it can hold parasitic DNA that does not benefit it in anything and still survive - DNA that takes a ride on DNA that is useful to the organism.

  4. The carnival cheers of the decoding of the human genome ignored a very significant point. The parts of the DNA that were not identified as genes, and they make up the majority of the text/letters, were unfortunately defined as unnecessary and some were quick to give them the title of junk DNA. There is something presumptuous in attributing such gross mistakes to nature. Now that we are calm we can perhaps check the functions of the Junk signal which probably serves as a control and also as a commander for the expression of genes in certain situations.

  5. The title is misleading and populist. It is clear that the project is a success because thousands of genomes of viruses, bacteria, and eukaryotes have been mapped to date, the information collected is invaluable and its implications for research are enormous. All the advanced technologies of chip on chip, microarrays and others that are today a cornerstone in research would not have been possible without the sequencing of genomes. Therefore, it is impossible to come and say, as implied in the title, that the project failed.
    True, as stated in the article itself, it turns out that the complexity is enormous and there are epigenetic effects that are difficult to predict from the sequence itself, but even the study of these phenomena is not possible without the complete sequencing of the genomes.

  6. I still don't fully understand, is the genome sequence mapped in this project the genetic sequence of one specific person? That is, they took genes from a sample skin cell of a certain person, read all the letters in the genome one by one and wrote them down in an orderly list?

    Or did they read a genetic sequence which is some kind of genetic average from genes taken from hundreds of thousands of people?


  7. So it turns out that genetics predicts diseases in a few percentages. It is likely that the environment and diet will not explain diseases in significant percentages either.
    It is possible that in the future the prediction will improve to a certain extent, by using models that combine the following factors into account, and will do so more successfully in diseases that are not mental illnesses.
    But the prediction will still be at a low level of probability, and there will remain an unexplained gap compared to the concrete reality of the individual person. Illness is also a matter of chance/fate/correction - depends on the observer's view.
    But according to the current course of things, one can at least hope that the healing capabilities offered by medicine, and genetic engineering in particular, will be at much higher levels, in the not so distant future.

  8. When we come to investigate the genetic "contribution" to the development of mental illnesses (and possibly other conditions as well) we must take into account not only the genetic variation itself that contributes to the disease. These also include the effect of the expression of genetic variation in another person on the person being studied. For example, a mother who developed schizophrenia thanks to the same genetic predisposition will raise the possibility, through her environmental influence on her children, that one of them will also develop schizophrenia. Even with the same genetic component, it was not inherited.
    The game of heredity-environment in these situations is more subtle and the statistical analyzes and studies must be adjusted accordingly.

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