Monologue about genetics
The Gene HunterMarina Muravyeva
Under the guidance of a well–known Russian geneticist, professor of the Faculty of Bioengineering and Bioinformatics of Moscow State University, head of three laboratories - at the Scientific Center of Mental Health of the Russian Academy of Medical Sciences, the Institute of General Genetics named after N.I.Vavilov of the Russian Academy of Sciences and at the Massachusetts Institute of Technology, Doctor of Biological Sciences Evgeny Ivanovich Rogaev, genes responsible for the development of Alzheimer's disease were found for the first time in the world, the gene of baldness was discovered, the remains of the family of Nicholas II were identified, the mammoth genome was sequenced (not the whole, but only the mitochondrial – VM) ... The scientist tells about these and other works on the pages STRF.ru .
Now is an interesting time for genetics. "A few years ago, I was thinking of changing the field of research and doing, for example, cell biology," Evgeny Rogaev admitted at a public lecture at Lomonosov Moscow State University ("Genomics in solving problems of medicine, the evolution of history"). — But with the development of fundamentally new methods of genomic sequencing and genetic analysis, it became clear: new prospects have opened up for genetics. In the future, it may not be necessary to carry out genetic mapping of genes, direct sequencing of the human genome will be quite effective to determine its genetic status."
There is every reason for such prospects, the question is in the cheapening of technologies. Sequencing the first human genome cost three billion dollars, the mouse genome cost 300 million, and the cow genome cost 30 million. Now the human genome can be sequenced for 30-40 thousand dollars. And this cost will gradually decrease.
First of all, scientists are interested in variations — how the genomes of different people differ, which mutations, polymorphisms cause diseases. There are more than 10 million different types of polymorphisms. From 12 to 20 percent of the genome of a human population can be affected by such types of changes. Their study in the field of criminology and forensic medicine is especially promising.
About mammoths and ancient DNAThe variety of animals in which the genome is sequenced is quite large.
There are some national projects. The genomes of grapes, kangaroos, etc. are being sequenced. Although successful sequencing of a particular genome is constantly being announced, as Professor Rogaev notes, today there is complete information about only six genomes. The rest are not fully tested, constructed.
In the 80-90s of the twentieth century, it became clear that DNA could be extracted from fossil objects. Over the past time, many studies have been conducted on DNA obtained from paleontological and historical samples. So, scientists led by Rogaev a few years ago managed to sequence the genome of a mammoth that lived more than 30 thousand years ago. The DNA in the nuclei of the cells was so well preserved that it could be detected with a fluorescent dye. For such an ancient paleontological specimen, this was shown for the first time.
The scientists worked with mitochondrial DNA, which is better preserved than nuclear DNA. (Mitochondria — cellular organelles responsible for supplying cells with energy — have their own genome — ed.)
"The number of copies of the mitochondrial genome is usually large, so it's easier to work," explained Evgeny Rogaev. — Let's say the muscle we dealt with in a mammoth contained about a thousand copies per cell. The work had quite a big resonance, because it demonstrated that it is possible to isolate and determine the DNA sequence without errors. In addition, we have identified a full-sized mitochondrial mammoth genome (Mitochondrial Genome), and this is not a hundred nucleotides or two hundred, but more than 16 thousand nucleotides, which in itself is of significant interest."
The analysis made it possible to answer a question that has been causing lively discussions for a long time: in the scientific community: which species is the mammoth closer to — Indian elephants or African elephants. Calculations have shown that the Indian elephant and mammoth are closer, sister species, and they had a common ancestor that departed from the ancestor of the African elephant.
About the Emperor's familyThe work with ancient DNA allowed Rogaev's group to conduct a large-scale study related to the identification of the remains of the Romanov family, which was shot in Yekaterinburg in 1918.
In the early 90s, the first burial was discovered, and in 2007 - the second. Evgeny Rogaev and his colleagues were asked to identify the fragments found in both graves, analyze the genetic material of the alleged remains of Nicholas II, his wife Alexandra Feodorovna and five children.
"The provided samples of the material at first glance seemed absolutely unsuitable for analysis,— said Evgeny Rogaev. — The bones were burned and possibly doused with sulfuric acid, in addition they had a loose, spongy structure: the worst case for DNA analysis. Nevertheless, we used maximally preserved areas of bone fragments. Small amounts (hundreds of milligrams) of bone tissue were thoroughly cleaned of possible impurities and ground into powder. The upper part of the bone fragments was removed, which turned out to be a difficult task: to remove too much — to lose precious material, and not enough — to risk contamination. Nevertheless, we were able to build almost complete mitochondrial genomes of the queen and her children (using specially developed technology)."
The mitochondrial genome of Alexandra Fyodorovna coincided with the genome of her distant maternal relatives (almost 17 thousand nucleotides completely coincided). This showed that the scientists were on the right track. Similar work was carried out with the remains of Nicholas II. To make sure of the result, it was necessary to analyze the Y chromosome (this had not been done before). The descendants of the Romanovs are famous people, kindly agreed to provide scientists with samples of their blood, in addition, a blood test was conducted of other people who are also carriers of the male Y chromosome. It turned out that they completely coincide.
Scientists were lucky: there was an opportunity to examine the shirt of Nicholas II with traces of his blood. In 1891, during the circumnavigation of the heir to the throne, an attempt was made on his life in Japan. All these years, Nikolai's shirt with bloodstains was kept in the Hermitage. The museum staff allowed Evgeny Rogaev to take DNA samples, which turned out to be extremely clean. The analysis showed that this sample completely coincides with the DNA extracted from the bone fragments of the burial.
"To date, we have a complete match of the DNA extracted from the bone remains and the shirt," concluded Professor Rogaev. "The accuracy of the data obtained is millions of times higher than, for example, fingerprint data."
About the royal blood diseaseIn parallel with the identification of the remains of the Romanov family, scientists managed to make another discovery: to establish an accurate diagnosis of the blood disease of the descendants of the British Queen Victoria, including the Russian Tsarevich Alexei.
DNA analysis clarified the origin of the disease that haunted members of the Russian and British families of monarchs in the late XIX — early XX century and was popularly called the "royal blood disease". The non-coagulability of blood, which many descendants of Queen Victoria of England suffered from, referred to the acute form of hemophilia B.
Using genetic material from bones found in Yekaterinburg, scientists have identified a mutation of the X chromosome, which is responsible for the production of blood factor IX, on which blood clotting depends. Since this disease is associated with an X-chromosome defect, it is transmitted through the maternal line only to men. This is because men have only one X chromosome. Women have two of them, and if one of them has a mutation, the second almost never duplicates it. Because of this, women are only transmitters of a genetic defect, but they themselves do not suffer from hemophilia B.
Thus, it was established that the heir to the throne, Alexei Romanov, received an illness from his mother, Empress Alexandra Feodorovna (born Alice Victoria Elena Louise Beatrice of Hesse-Darmstadt), who was the granddaughter of Queen Victoria of England.
About the genes of baldnessAnother mutant gene, which was discovered by the group of Evgeny Rogaev, is associated with baldness.
As the scientist noted, they were interested not so much in mutations of the genes responsible for baldness, as in the processes behind it: "The hair follicle is an interesting mini—organ. Hair follicle cells multiply millions of times faster and more actively than tumor cells, and, in addition, they are subject to cyclical changes: for a certain time (from 2 to 8 years), hair grows, then comes a phase when active growth slows down, and finally, a period when hair falls out. By studying these cyclic processes, it is possible to determine the molecules or factors that are responsible for regenerative processes: hair follicle cells have an amazing regenerating ability and, apparently, are used in the body for healing skin wounds."
Professor Evgeny Rogaev managed to discover the gene responsible for hair growth based on the results of almost ten years of research initiated by the Director of the Medical and Genetic Research Center of the Russian Academy of Medical Sciences Evgeny Ginter. In some territories of the Volga-Ural region, scientists have identified many cases of hereditary hypotrichosis (a disease in which hair grows poorly or actively falls out). To identify the genetic causes of the disease, 350 thousand residents were examined and using the methods of positional gene cloning, mutations in any gene cause baldness were determined. The damaged gene turned out to be the LIPH phospholipase gene (lipase H), which is involved in the production of the simplest lipids — organic substances that are responsible for many biological functions in the body.
Further studies have shown that the phospholipase gene is expressed in hair follicles and, in particular, works in the part where stem cells are located (it is thanks to them that hair grows all its life). Phospholipase of hair follicles breaks down lipid molecules into small lipids, which affect the division and migration of stem cells, and thereby hair growth.
Scientists have tried to obtain a substance that can be chemically synthesized, and which promotes hair growth. The first tests conducted on mice showed a good result. The research will continue.
About mysterious diseasesIn genetics, there are two approaches to the study of diseases, which can be called monogenic and polygenic.
Most of the successes are associated with the identification of genes of monogenic diseases, which are quite easily isolated. However, most diseases are associated not only with genetic factors, but also with social ones.
Evgeny Rogaev was the first in the world to discover the genes responsible for the development of Alzheimer's disease, the main sign of which is memory loss and the formation of amyloid plaques in the brain. (see the article "When genes drive you crazy"). Over the past 20 years, the main genes of the disease have been discovered.
With regard to another disease — schizophrenia, it is not necessary to talk about great achievements, stated Professor Rogaev. Until now, this disease is considered the most mysterious. The role of genetic factors is about 40 percent, respectively, the role of the environment is extremely important in the development of pathology. Recent studies have shown that about one and a half percent of schizophrenics have deletions in the regions of chromosomes 1,12, 22. That is, for 99 percent of cases of schizophrenia, genes are unknown, therefore, new genomic approaches need to be used to identify them.
Why do I need to know polymorphisms, mutations? First of all, for preclinical research, Evgeny Rogaev summarized some results. The next aspect is pharmacogenetics. It is necessary to know the genetic characteristics of a person in order to recommend a particular drug for treatment. Naturally, factors such as smoking and caffeine affect the absorption of medications. These factors are rarely taken into account in medicine. But this is the future. Finally, knowledge about genes is essential in the development of therapeutic agents.
Portal "Eternal youth" http://vechnayamolodost.ru30.12.2009