Twins disappointed geneticists
Troubles in the genomic kingdom
Twin brothers have presented a new mystery for scientistsAlexander Spirin, Nezavisimaya Gazeta
We have quietly entered the era of genomic research, which has also invaded medicine unobtrusively.
Leroy Hood, one of the heroes of the famous Human Genome project, published with his colleagues at the Institute of Systems Biology in Seattle and the University of Utah in Salt Lake City the results of the analysis of the genomes of four family members.
The study of the genomes of parents and their two children revealed the "hot spots" of recombination, in which there is an active exchange of sections of the chromosomes of the father and mother, 70% of errors that occurred during DNA copying, as well as rare snips, that is, single nucleotide differences that have not yet been known to science. The frequency of mutations between the parental and child generations of people was also quantified for the first time. It was 1:100 million.
The interest in the complete genomes of members of this family is due to the fact that both children suffer from two disorders, the genes of which are already known. A full-scale genomic analysis has narrowed the number of gene candidates to just four, which will put further research on a solid foundation.
Stanford University researchers Irina Hrebtukova and Elena Ganusova decided to approach the study of the genetic basis of human disease from the standpoint of the classical method of human genetics, that is, the study of identical, or identical, twins. Their genomes represent an ideal "polygon", because, on the one hand, they are so identical that all kinds of transplants are possible due to the absence of a rejection reaction from the immune system. At the same time, it is well known that twins are still different, because, for example, they age differently.
Scientists analyzed the state of the genomes of three pairs of twins, one of whom suffers from multiple sclerosis, and the other or the other is healthy. The first couple was represented by Ashkenazi sisters, one of whom fell ill at the age of 30. The second couple is African–American (38 years old), the third is white brothers, one of whom started sclerosis at the age of 13. As follows from the theory, the regions of the genomes that are responsible for rejection had identical genotypes in twins.
Scientists have fully read the genome of Ashkenazi women, discordant – "mismatched" – for the development of sclerosis, which is an autoimmune disease. 3.6 million were also identified . snips and 200 thousand larger differences in genomes in the form of insertions and non-insertions-deletions. In addition, the activity of 19 thousand genes of the so-called T4 lymphocytes (helpers) was determined, with the activation of which the immune response begins and which are primarily infected with HIV. These same cells are involved in the development of pathophysiological changes leading to the development of multiple sclerosis. Genomic diagnostics has been confirmed not only by clinical, but also by NMR studies, as well as analyses of spinal fluid.
The discouraging conclusion drawn from the results of the gigantic work indicates that the genomes of discordant twins do not differ in any way. 176 epigenomic differences were revealed in three couples, only two of which were noted in healthy and sick sisters. This, of course, is negligible to say something definite about the mechanisms of development of such a serious disease. Suffice it to say that there are up to 800 differences between T-lymphocytes of unrelated healthy people, which cause a rejection reaction. And between different tissues of the body or between healthy cells and cancerous, the number of differences is even greater – several thousand.
What can I say about this. The euphoria of scientists associated with the completion of reading the human genome at the beginning of the genomic millennium has clearly faded. Another evidence of its unjustifiability is the results of this study. Something is wrong in the genomic kingdom: either there is a lack of sensitivity of the methods used, or this approach is fundamentally wrong. Critics have been talking about this since 2007.
However, an undetected discordance at the molecular level may also indicate our lack of understanding of the nature of the development of diseases. Perhaps, indeed, the two non-mutant differences found by scientists play an important role in the further growth of the pathological cascade. Further analysis, more thoughtful and unhurried, will allow you to see what was missed with the natural desire to publish as soon as possible, to stake out an undoubtedly gold-bearing site.
This disappointment is quite comparable to what scientists experienced in the 80s of the last century, when many oncogenes were discovered, but this discovery did not give anything to practical oncology. Then everyone dreamed: if only we had a genome. Today we already have a lot of genomes, and who – at least cancer – is still there…
Portal "Eternal youth" http://vechnayamolodost.ru25.06.2010