Protection against deadly mutations: details

When harmful mutations become harmless

Kirill Stasevich, "Science and Life" based on the materials of The Scientist: Genetic Resilience

Mutations that cause severe genetic diseases sometimes remain without consequences – for reasons that are not entirely clear.

Genetic analysis makes it possible to predict the development of a particular disease with a certain degree of probability. Genes, as we know, contain information about proteins, and no molecular process in a cell can do without proteins: with their help we get energy, they also synthesize other biological macromolecules, such as lipids and nucleic acids, etc., etc. If a mutation gets into any gene, then the enzyme encoded by it will not work exactly as it should, or will not work at all, and in this case you should think about how to live with it: what to eat, what not to eat, what kind of sports to do, and so on, and so on. Of course, not all of our DNA is occupied by protein-coding sequences, it has a lot of regulatory sites that control the activity of other genes, but the essence of the matter in this case remains the same – a defect in some regulatory fragment can affect health in the same way as a mutation in the protein-coding region.

Of course, the medical prognosis depends on the importance of the gene, which is determined by its "occupation". And then we can assume that mutations that completely disable some important gene will lead to extremely serious consequences, which should be confirmed by medical statistics. However, just in the statistics over time, amazing cases began to appear when people with a seemingly pathogenic mutation have no signs of the disease. (We wrote about one of these studies just a month ago.) Perhaps the most outstanding example in this sense is a recent article in Nature Biotechnology, the authors of which purposefully searched for those who definitely have pathogenic mutations in their genome, but with whom nothing bad ever happened. Stephen H Friend and his colleagues from Mount Sinai Medical Center, Beijing Institute of Genomics, Lund University and other research centers used data from 12 large-scale genomic projects (including data from the well-known biotechnology company 23andMe, which performs genetic analyses for private customers). The number of analyzed genomes was about 590 thousand; researchers were interested in several hundred genes, mutations in which threatened serious consequences. At first, it was possible to find 15,000 people who, for some reason, turned out to be immune to genetic defects; more careful selection reduced their number to only 13. Each of the thirteen had some extremely dangerous mutation that should have caused cystic fibrosis, or Smith-Lemley-Opitz syndrome associated with a violation of cholesterol synthesis, or some other equally serious disease. However, we repeat, they were all healthy, at least, judging by the data available to the authors of the work.

Here it is necessary to clarify that the researchers did not see the carriers of mutations themselves in this case – the rules of such studies do not allow finding a specific person whose genome interested everyone so much. In the case of eight out of thirteen "mutants", there is a possibility that their DNA was read with an error, seeing a mutation where it does not exist – and it is impossible to double-check it. It is also impossible to check their clinical condition, that is, whether they really do not have the diseases that should occur with such mutations.

Nevertheless, the question still remains how the body manages to avoid genetic diseases in such cases. Two people who should have had Smith-Lenly-Opitz syndrome due to gene damage found several more variants of the same gene in their genomes, which apparently saved the situation. It is possible that in other cases it was all about additional copies of certain genes, but it is not yet possible to verify this assumption in detail. Genomes are not always read from beginning to end, in most cases, only areas of interest to doctors or the client are selected for sequencing, about which it is reliably known that obesity genes, or diabetes genes, or genes of some hereditary disease are sitting here. It is possible that gene backups are not the only way to avoid the negative effects of mutations, and that genes may have different systems to "back up" each other, but in order to find them, more genetic data is needed.

Portal "Eternal youth" http://vechnayamolodost.ru  13.04.2016