Modern research in molecular genetics. Genetics • big Russian encyclopedia - electronic version. Genetics in agriculture

If the 19th century rightfully entered the history of world civilization as the century of physics, then the 20th century I, in which we were happy to live, in all likelihood, is destined for the age of biology, and perhaps genetics.

The middle and second half of the 20th century were marked by a significant decrease in the frequency and even the complete elimination of a number of infectious diseases, a decrease in infant mortality, and an increase in average life expectancy. In the developed world, the focus of health services has shifted to the fight against chronic human pathology, diseases of cardio-vascular system, oncological diseases.

It became obvious that progress in the field of medical science and practice is closely related to the development of general and medical genetics and biotechnology. The amazing achievements of genetics have made it possible to reach the molecular level of knowledge of the genetic structures of the body, and inheritance, to reveal the essence of many serious human diseases, to come close to gene therapy.

Clinical genetics has been developed - one of the most important areas of modern medicine, acquiring a real preventive value. It turned out that many chronic human diseases are a manifestation of a genetic burden, the risk of their development can be predicted long before the birth of a child, and practical opportunities have already appeared to reduce the pressure of this burden.

In February 2001, two of the world's most authoritative scientific journals, Nature and Science, published reports from two scientific groups that had deciphered the human genome. The journal "Nature" dated February 12, 2001 provides detailed data on the structure of the human genome, obtained by an international consortium led by Francis Collins, in which scientists from England, Germany, China, the USA, France and Japan worked within the framework of the international program "Human Genome" with attracting public funding. This group isolated special markers in DNA, easily recognizable regions, and determined the nucleotide sequences of the human genome using them. In the journal "Science" dated February 16, 2001, scientists from the private firm "Celera Genomics" led by Craig Venter published the results of the decoding of the human genome, obtained using a different research strategy, which is based on the analysis of nucleotide base sequences in short sections of human DNA. Thus, when deciphering the human genome, two scientific approaches were used, each of which has its own advantages and disadvantages. It is important to note that closely coinciding results were obtained, which complement each other and testify to their reliability. The question of the accuracy of the study of DNA sequences is especially important in relation to the human genome. There are a large number of nucleotide repeats in our genome. In addition to them, chromosomes contain telomeres, centromeres, and heterochromatin zones, where sequencing is difficult and they have so far been excluded from studies. A preliminary analysis of published materials on the decoding of the human genome allows us to note several features. The number of genes in a person turned out to be significantly less than scientists thought a few years ago, naming values ​​of 80-100,000 genes. According to data published in the journal Nature, humans have about 32,000 genes, while the fruit fly has 13,000, the nematode roundworm has 19,100, and the Arabidopsis plant has 25,000 genes. When comparing these values, it should be borne in mind that the estimated number of human genes was obtained by computer genomics, and not all genes have end products. In addition, the principle of "one gene - many proteins" operates in the human genome, that is, many genes encode a family of related, but significantly different proteins. One should also keep in mind the process of post-translational modification of proteins due to various chemical groups - acetyl, glycosyl, methyl, phosphate, and others. Since there are many such groups in a protein molecule, the diversity can be practically unlimited. Another feature of the human genome is the presence in it of the genes of various viruses and bacteria, which gradually accumulated in the course of the multimillion-year human evolution. According to the figurative expression of Academician L.L. Kiseleva, "... the human genome is a molecular graveyard on which viral and bacterial genes rest, most of them are silent and do not function."

According to recent estimates of the International Service for the Implementation of Applied Biotechnology in Agriculture, the area under "genetic" crops and the production of genetic cereal products are increasing by 25-30% every year.

But so far, the EU member states have not decided on the prospects for genetic technologies in agriculture and Food Industry. And the temptation is great: according to the French microbiologist Jean-Paul Prunier, “by manipulating molecules and inoculating one plant with the cells of another, including artificially grown, one can obtain a wide variety of fruits, vegetables, cereals and root crops. Moreover, high-yielding, almost immune to diseases , pests, lack of water and light or drought."
For example, about 50 types of genetic products from genetic corn and 10 from genetic cereals are currently consumed in France. Moreover, the latter are already beginning to displace traditional rapeseed, cotton, corn, soybeans, fodder grasses and even vineyards there, as well as in the French overseas territories.

Determination of paternity by DNA diagnostics

The carrier of human hereditary information is DNA. In each person, it is located in 46 paired chromosomes. A person receives 23 chromosomes from the mother, the remaining 23 from the father. The numbering of each pair is made in accordance with the international classification, while the differences between pairs of chromosomes are visually detected using a microscope; the chromosomes of each pair, except for the X and Y sex chromosomes, are considered the same.

However, modern molecular genetic methods make it possible to individualize each chromosome of a pair. This allows you to determine paternity at the DNA level.

When establishing paternity, individual differences in the DNA of certain paired chromosomes are examined. First, it turns out which chromosome from the pair the child received from the mother, then the remaining chromosome is compared with the chromosomes of the alleged father.

Other possibilities of modern genetics

To date, a wide range of genes has been identified, the unfavorable variants of which can mediate the occurrence of preeclampsia, based on the currently known possible ways development of endothelial dysfunction underlying its pathogenesis. The genetic component of preeclampsia includes not only maternal but also fetal genetic polymorphism and can account for up to 50% of all factors influencing the development of preeclampsia; first of all, these are genes of the main histocompatibility complex, genes of cytokines and growth factors, genes of vasoactive substances synthesized by the endothelium, genes of the hemostasis system, genes of vascular tone and genes of the antioxidant system.

Today, scientists believe that almost all diseases are determined by hereditary factors that manifest themselves in certain environmental conditions. We give information to a person about a variant (favorable or unfavorable) of a gene of predisposition to a certain disease. It is important to understand that the genetic passport helps to predict the possibility of the occurrence of the disease, and not its 100% occurrence. Knowing about the genetic predisposition, you can adjust your lifestyle in such a way as to reduce the likelihood of developing the disease.

The study of the genes responsible for high sports achievements is of great importance for professional athletes. In our laboratory, DNA certification of athletes is carried out according to a complex of 20 main genes that have a significant impact on the state of the musculoskeletal system, endurance, speed, strength, adaptation to hypoxia, and the ability to recover from physical exertion. Studying, for example, the propensity for hypoxia (oxygen starvation) in the Olympic biathlon team of Belarus, we identified not very desirable genes in some of them, thanks to which it was possible to correct the training process and optimize the load.

At the Institute of Rheumatology, systematic studies of the structure of hereditary predisposition to rheumatic diseases have been carried out over the past 25 years using genealogical, twin, population genetic, immunogenetic and molecular genetic research methods.

The conducted studies, as well as the work of foreign authors, have shown that the contribution of genetic factors to the determination of rheumatic diseases prevails over the contribution of environmental factors. This opens the prospect of searching for genes of predisposition to rheumatic diseases using the methodology of "reverse genetics". The strategy of "reverse genetics" in relation to the search for predisposition genes at the first stage implies their localization on a specific region of a particular chromosome (i.e., mapping) using linkage analysis with genetic markers whose chromosomal localization is already known. Linkage analysis is a test for the joint or independent inheritance of a disease and genetic markers in families. The closer the disease predisposition gene and genes of genetic markers are located on the chromosome, the more often they are inherited together in pedigrees, which makes it possible to determine the chromosomal localization of the sensitivity gene using recombination frequency indicators between them. A quantitative indicator of linkage is the logarithm of the odds ratio for and against its presence in the surveyed family - lod-point. The total value of LOD scores for the sample of families equal to +3.0 or more (which corresponds to the probability p=0.001 or less) indicates the presence of linkage, while the value of -2.0 or less indicates its absence.

Two main approaches are used to identify a susceptibility gene using linkage analysis:

A) candidate genes for the role of the main gene are selected and their polymorphism in informative families is examined, followed by calculation of lod-points, and the negative value of this indicator (-2.0 or less) makes it possible to unequivocally exclude the candidate gene from the candidates for the role of the main gene;

B) polymorphic, sufficiently informative (with a high level of heterozygosity) DNA markers (from 15 or more per chromosome) are selected, families are tested, followed by an analysis of the link between the disease and all markers used. The values ​​of lod-scores obtained as a result of such an analysis help to determine the segment of the chromosome in which the gene of predisposition to the disease can be localized.

Thus, the methodology of "reverse genetics" opens up opportunities for the search for predisposition genes, without prior information about their number, function and significance in the etiopathogenesis of the disease.

Within the framework of the above methodology, a broad search for susceptibility genes for a number of rheumatic diseases has been carried out in recent years. For example, Shiozawa et al. (1997) screened all chromosomes in families with recurrent cases of rheumatoid arthritis using 358 polymorphic DNA markers for this purpose. As a result of the work carried out by linkage analysis, two regions on the X chromosome that are promising for the search for genes of sensitivity to rheumatoid arthritis were identified, in which the tumor necrosis factor receptor gene and the CD40 ligand gene are localized, which, according to the authors, are candidate genes of predisposition to PA. F. Cornelis et al. (1997), using a similar methodology, identified two critical chromosomal regions whose markers are linked to rheumatoid arthritis and may contain disease susceptibility genes. One of these regions is located on the X chromosome (localization corresponds to the data of Japanese authors), while the other is located in the same segment of the 3rd chromosome as the IDDM9 gene, which is one of the genes that determine sensitivity to insulin-dependent diabetes. According to the authors, the contribution of this gene to the determination of the disease is about 27%.

Introduction
Genetics can rightly be considered one of the most important areas of biology. For thousands of years, man has used genetic methods to improve the useful properties of cultivated plants and breed highly productive breeds of domestic animals, without having an understanding of the mechanisms underlying these methods. Judging by the various archaeological data, already 6000 years ago people understood that some physical signs could be transmitted from one generation to another. By selecting certain organisms from natural populations and crossing them with each other, man created improved varieties of plants and animal breeds that possessed the properties he needed.
However, only at the beginning of the 20th century, scientists began to fully realize the importance of the laws of heredity and its mechanisms. Although the advances in microscopy made it possible to establish that hereditary traits are transmitted from generation to generation through spermatozoa and eggs, it remained unclear how the smallest particles of protoplasm could carry the "inclinations" of the vast array of traits that make up each individual organism.
Genetics took shape as a science after the rediscovery of Mendel's laws. memorable date in biology was the spring of 1953. Researchers American D. Watson and Englishman F. Crick deciphered the "holy of holies" of heredity - its genetic code. It was from that time that the word "DNA" - deoxyribonucleic acid became known not only to a narrow circle of scientists, but to every educated person all over the world. The turbulent century-long period of its development was marked in recent years by the deciphering of the nucleotide composition of the "life molecule" of DNA in dozens of species of viruses, bacteria, fungi and multicellular organisms.
The sequencing (establishing the order of alternation of nucleotides) of the DNA of chromosomes of important cultivated plants - rice, corn, wheat - is in full swing. At the beginning of 2001, it was solemnly announced the fundamental decoding of the entire human genome - DNA, which is part of all 23 pairs of chromosomes of the cell nucleus. These biotechnological advances have been compared to going into space.
Deoxyribonucleic acid, or DNA, was first isolated from cell nuclei. Therefore, it was called nucleic (Greek nucleus - core). DNA consists of a chain of nucleotides with four different bases: adenine (A), guanine (G), cytosine (C), and thymine (T). DNA almost always exists in the form of a double helix, that is, it consists of two nucleotide chains that make up a pair. What holds them together is what is known as base pair complementarity. "Complementary" means that when A and T are opposite each other in two strands of DNA, a bond is spontaneously formed between them. Similarly, a complementary pair is formed by G and C. Human cells contain 46 chromosomes. The length of the human genome (all the DNA in the chromosomes) can reach two meters and consists of three billion nucleotide pairs. A gene is a unit of heredity. It is part of a DNA molecule and contains encoded information about the amino acid sequence of a single protein or ribonucleic acid (RNA).
The message of scientists that they managed to decipher the structure of this large molecule brought together the previously disparate results of research in biochemistry, microbiology and genetics, conducted over half a century. In recent decades, mankind has been observing the rapid progress of genetics. This science has long become the most important asset of mankind, to which the hopes of millions of people are turned.
I. The subject of genetics
Just as in physics the elementary units of matter are atoms, in genetics the elementary discrete units of heredity and variability are genes. The chromosome of any organism, be it a bacterium or a human, contains a long (hundreds of thousands to billions of base pairs) continuous DNA chain along which many genes are located. Establishing the number of genes, their exact location on the chromosome, and the detailed internal structure, including knowledge of the complete nucleotide sequence, is a task of exceptional complexity and importance. Scientists successfully solve it using a whole range of molecular, genetic, cytological, immunogenetic and other methods.
An important feature of eukaryotic genes is their discontinuity. This means that the region of the gene encoding the protein consists of two types of nucleotide sequences. Some - exons - sections of DNA that carry information about the structure of the protein and are part of the corresponding RNA and protein. Others - introns - do not encode the structure of the protein and are not included in the composition of the mature mRNA molecule, although they are transcribed. The process of cutting out introns - "unnecessary" sections of the RNA molecule and splicing of exons during the formation of mRNA is carried out by special enzymes and is called splicing (crosslinking, splicing). Exons are usually joined together in the same order as they are in DNA. However, not all eukaryotic genes are discontinuous. In other words, in some genes, like bacteria, there is a complete correspondence of the nucleotide sequence to the primary structure of the proteins they encode.
Representatives of any biological species reproduce creatures similar to themselves. This property of descendants to be similar to their ancestors is called heredity.
Despite the enormous influence of heredity in shaping the phenotype of a living organism, related individuals differ to a greater or lesser extent from their parents. This property of descendants is called variability. The science of genetics deals with the study of the phenomena of heredity and variability. Thus, genetics is the science of the laws of heredity and variability. According to modern concepts, heredity is the property of living organisms to transmit from generation to generation features of morphology, physiology, biochemistry and individual development under certain environmental conditions. Variability - a property opposite to heredity - is the ability of daughter organisms to differ from their parents in morphological, physiological, biological characteristics and deviations in individual development. Heredity and variability are realized in the process of inheritance, i.e. when transferring genetic information from parents to offspring through germ cells (during sexual reproduction) or through somatic cells (during asexual reproduction).
Genetics as a science solves the following main tasks:
· studies ways of storing genetic information in different organisms (viruses, bacteria, plants, animals and humans) and its material carriers;
analyzes the ways of transferring hereditary information from one generation of organisms to another;
· reveals the mechanisms and patterns of implementation of genetic information in the process of individual development and the impact on their environmental conditions;
· studies patterns and mechanisms of variability and its role in adaptive reactions and in the evolutionary process;
Finds ways to correct damaged genetic information.
To solve these problems, different research methods are used.
The method of hybridological analysis was developed by Gregor Mendel. This method makes it possible to reveal patterns of inheritance of individual traits during sexual reproduction of organisms. Its essence is as follows: the analysis of inheritance is carried out on separate independent traits; transmission of these signs in a number of generations is traced; an accurate quantitative account is taken of the inheritance of each alternative trait and the nature of the offspring of each hybrid separately.
The cytogenetic method allows you to study the karyotype (set of chromosomes) of body cells and identify genomic and chromosomal mutations.
The genealogical method involves the study of pedigrees of animals and humans and allows you to establish the type of inheritance (for example, dominant, recessive) of a particular trait, the zygosity of organisms and the likelihood of manifestation of traits in future generations. This method is widely used in breeding and the work of medical genetic consultations.
The twin method is based on the study of the manifestation of signs in identical and dizygotic twins. It allows you to identify the role of heredity and the environment in the formation of specific traits.
Biochemical research methods are based on the study of the activity of enzymes and chemical composition cells that are determined by heredity. Using these methods, it is possible to identify gene mutations and heterozygous carriers of recessive genes.
The population-statistical method makes it possible to calculate the frequency of occurrence of genes and genotypes in populations.
Let us introduce the basic concepts of genetics. When studying the patterns of inheritance, individuals are usually crossed that differ from each other in alternative (mutually exclusive) traits (for example, yellow and green color, smooth and wrinkled surface of peas). Genes that determine the development of alternative traits are called alleles. They are located in the same loci (places) of homologous (paired) chromosomes. An alternative trait and the gene corresponding to it, which appears in hybrids of the first generation, are called dominant, and not manifested (suppressed) are called recessive. If both homologous chromosomes contain the same allelic genes (two dominant or two recessive), then such an organism is called homozygous. If different genes of the same allelic pair are localized in homologous chromosomes, then such an organism is usually called heterozygous for this trait. It forms two types of gametes and, when crossed with an organism of the same genotype, gives splitting.
The totality of all the genes of an organism is called the genotype. A genotype is a set of genes that interact with each other and influence each other.
Each gene is affected by other genes of the genotype and itself affects them, so the same gene in different genotypes can manifest itself in different ways.
The totality of all the properties and characteristics of an organism is called the phenotype. The phenotype develops on the basis of a certain genotype as a result of interaction with environmental conditions. Organisms with the same genotype may differ from each other depending on the conditions of development and existence. A single feature is called a hair dryer. Phenotypic features include not only external features (eye color, hair, nose shape, flower color, etc.), but also anatomical (stomach volume, liver structure, etc.), biochemical (glucose and urea concentration in blood serum, etc.). ) other.

II. Heredity. Mendel's research
An important step in the knowledge of the laws of heredity was made by the outstanding Czech researcher Gregor Mendel. He revealed the most important laws of heredity and showed that the characteristics of organisms are determined by discrete (individual) hereditary factors. The work “Experiments on plant hybrids” was distinguished by depth and mathematical accuracy, but it was published in the little-known works of the Brunn Society of Naturalists and remained unknown for almost 35 years - from 1865 to 1900. It was in 1900. G. de Vries in Holland, K. Korrens in Germany and E. Cermak in Austria independently rediscovered Mendel's laws and recognized his priority. The rediscovery of Mendel's laws caused the rapid development of the science of heredity and variability of organisms - genetics.
The success achieved by Mendel is partly due to the successful choice of the object for experiments - garden peas (Pisum sativum). Mendel made sure that, compared to others, this species has the following advantages:
1) there are many varieties that clearly differ in a number of characteristics;
2) plants are easy to grow;
3) the reproductive organs are completely covered with petals, so that the plant usually self-pollinates; therefore, its varieties reproduce in purity, that is, their characteristics remain unchanged from generation to generation;
4) artificial crossing of varieties is possible, and it gives quite fertile hybrids.
Of the 34 varieties of peas, Mendel selected 22 varieties with distinct differences in a number of characteristics, and used them in his experiments with crossing. Mendel was interested in seven main characteristics: stem height, seed shape, seed color, fruit shape and color, and flower arrangement and color. It should be noted that in choosing an experimental object, Mendel was simply lucky in some ways: in the inheritance of the traits he selected, there were no more complex features discovered later, such as incomplete dominance, dependence on more than one pair of genes, gene linkage. This fact partly explains the fact that before Mendel, many scientists conducted similar experiments on plants, but none of them received such accurate and detailed data; moreover, they were unable to explain their results in terms of the mechanism of heredity.
For his first experiments, Mendel chose plants of two varieties that clearly differed in some way, for example, in the arrangement of flowers: flowers can be distributed throughout the stem (axillary) or located at the end of the stem (apical). Plants that differ in one pair of alternative traits were grown by Mendel over a number of generations. In all cases, the analysis of the results showed that the ratio of dominant to recessive traits in a generation was approximately 3:1.
The above example is typical of all Mendel's experiments in which the inheritance of one trait was studied (monohybrid crosses).
Based on these and similar results, Mendel concluded:
1. Since the original parental varieties were propagated in the pure (not splitting), the axillary flower variety should have two "axillary" factors, and the tip flower variety should have two "top" factors.
2. F1 plants contained one factor derived from each of the parent plants via gametes.
3. These factors in F1 do not merge, but retain their individuality.
4. The "axillary" factor dominates the "top" factor, which is recessive. The separation of a pair of parental factors in the formation of gametes (so that only one of them gets into each gamete) is known as the first law of Mendel or the law of splitting. According to this law, the characteristics of a given organism are determined by pairs of internal factors. Only one of each pair of such factors can be present in one gamete.
We now know that these factors, which determine traits such as the location of a flower, correspond to sections of the chromosome called genes.
The experiments described above, conducted by Mendel when studying the inheritance of one pair of alternative traits, serve as an example of monohybrid crossing.

III. Variability and influence of the environment. Types and significance of mutations.
Variability is the whole set of differences in one or another trait between organisms belonging to the same natural population or species. The astonishing morphological diversity of individuals within any species caught the attention of Darwin and Wallace during their travels. The natural, predictable nature of the transmission of such differences by inheritance served as the basis for Mendel's research. Darwin established that certain traits can develop as a result of selection, while Mendel explained the mechanism that ensures the transmission from generation to generation of traits for which selection is made.
Mendel described how hereditary factors determine the genotype of an organism, which in the process of development manifests itself in the structural, physiological and biochemical features of the phenotype. If the phenotypic expression of any trait is ultimately determined by the genes that control that trait, then the degree of development of certain traits can be influenced by the environment.
The main factor that determines any phenotypic trait is the genotype. The genotype of an organism is determined at the moment of fertilization, but the degree of subsequent expression of this genetic potential largely depends on external factors affecting the organism during its development. So, for example, the long-stemmed pea variety used by Mendel usually reached a height of 180 cm. However, for this he needed the appropriate conditions - lighting, water supply and good soil. In the absence of optimal conditions (in the presence of limiting factors), the tall stem gene could not fully manifest its effect. The effect of the interaction of the genotype and environmental factors was demonstrated by the Danish geneticist Johannsen.
In a series of experiments on dwarf beans, he selected the heaviest and lightest seeds from each generation of self-pollinating plants and planted them to produce the next generation. Repeating these experiments over several years, he found that within a "heavy" or "light" breeding line, the seeds differed little in average weight, while the average weight of seeds from different lines varied greatly. This suggests that the phenotypic manifestation of a trait is influenced by both heredity and the environment. Based on these results, continuous phenotypic variation can be defined as "the cumulative effect of varying environmental factors acting on a variable genotype". In addition, these results show that the degree of heritability of a given trait is determined primarily by the genotype. As regards the development of such purely human qualities as individuality, temperament and intelligence, judging by the available data, they depend on both hereditary and environmental factors, which, interacting to varying degrees in different individuals, create phenotypic differences between individuals. We do not yet have data that would firmly indicate that the influence of some of these factors always prevails, but the environment can never push the phenotype beyond the limits determined by the genotype.
It must be clearly understood that the interaction between discrete and continuous variability and the environment makes it possible for two organisms to exist with an identical phenotype.

The mechanism of DNA replication during mitosis is so close to perfection that the possibilities of genetic variability in organisms with asexual reproduction are very small. Therefore, any visible variability in such organisms is due to environmental influences. As for organisms that reproduce sexually, they have ample opportunities for the emergence of genetic differences. Almost unlimited sources of genetic variability are two processes that occur during meiosis:
1. Reciprocal exchange between chromatids of homologous chromosomes, which can occur in prophase 1 of meiosis. It creates new linkage groups, i.e. serves as an important source of genetic recombination of alleles.
2. The orientation of pairs of homologous chromosomes (bivalents) in the equatorial plane of the spindle in metaphase I of meiosis determines the direction in which each member of the pair will move in anaphase I. This operation is random. During metaphase II, the pairs of chromatids again orient themselves randomly, and this determines which of the two opposite poles one or another chromosome will go to during anaphase II. Random orientation and subsequent independent divergence (segregation) of chromosomes makes possible a large number of different chromosome combinations in gametes; this number can be calculated.

A third source of variability in sexual reproduction is that the fusion of male and female gametes, resulting in the union of two haploid sets of chromosomes in the diploid nucleus of the zygote, occurs in a completely random way (at least in theory); any male gamete has the potential to fuse with any female gamete.
These three sources of genetic variation provide the constant shuffling of genes that underlies the ongoing genetic change. The environment influences the whole range of phenotypes thus obtained, and those best adapted to the environment succeed. This leads to changes in the frequencies of alleles and genotypes in the population. However, these sources of variability do not give rise to large changes in the genotype, which, according to evolutionary theory, are necessary for the emergence of new species. Such changes result from mutations.
A mutation is a change in the amount or structure of DNA in a given organism. The mutation results in a genotype change that can be inherited by cells derived from the mutated cell through mitosis or meiosis. Mutation can cause changes in any traits in a population. Mutations that have arisen in germ cells are transmitted to the next generations of organisms, while mutations that have arisen in somatic cells are inherited only by daughter cells formed by mitosis and such mutations are called somatic.

Mutations resulting from changes in the number or macrostructure of chromosomes are known as chromosomal mutations or chromosomal aberrations (rearrangements). Sometimes the chromosomes change so much that it can be seen under a microscope. But the term "mutation" is used mainly to refer to a change in the structure of DNA at one locus, when a so-called gene or point mutation occurs.
The idea of ​​mutation as the cause of the sudden appearance of a new trait was first put forward in 1901 by the Dutch botanist Hugo de Vries, who studied heredity in evening primrose Oenothera lamarckiana. After 9 years, T. Morgan began to study mutations in Drosophila, and soon, with the participation of geneticists from all over the world, more than 500 mutations were identified in it.
Chromosomal and gene mutations have a variety of effects on the body. In many cases, these mutations are lethal because they interfere with development; in humans, for example, about 20% of pregnancies end in natural miscarriage before 12 weeks, and in half of these cases chromosomal abnormalities can be detected. Certain chromosomal mutations can bring certain genes together, and their combined effect can lead to the appearance of some kind of "favorable" trait. In addition, the proximity of some genes to each other makes them less likely to separate as a result of crossing over, and in the case of favorable genes, this creates an advantage.
Gene mutation can lead to that. That there will be several alleles at a particular locus. This increases both the heterozygosity of a given population and its gene pool, and leads to an increase in intrapopulation variability.
Gene shuffling as a result of crossing over, independent distribution, random fertilization, and mutations can increase continuous variation, but its evolutionary role is often transient, as the resulting changes can quickly be smoothed out due to "averaging". As for gene mutations, some of them increase discrete variability, and this can have a deeper effect on the population. Most gene mutations are recessive with respect to the "normal" allele, which, having successfully withstood selection over many generations, has reached genetic equilibrium with the rest of the genotype. Being recessive, mutant alleles can remain in the population for many generations until they manage to meet, i.e. be in a homozygous state and appear in the phenotype. From time to time, dominant mutant alleles can also occur, which immediately give a phenotypic effect.

IV. Treatment and prevention of certain human hereditary diseases
The increased interest of medical genetics in hereditary diseases is explained by the fact that in many cases knowledge of the biochemical mechanisms of development makes it possible to alleviate the suffering of the patient. The patient is injected with enzymes that are not synthesized in the body. For example, diabetes mellitus is characterized by an increase in the concentration of sugar in the blood due to insufficient (or complete absence) production of the hormone insulin by the pancreas in the body. This disease is caused by a recessive gene. Back in the 19th century, this disease almost inevitably led to the death of the patient. Getting insulin from the pancreas of some pets has saved the lives of many people. Modern methods of genetic engineering have made it possible to obtain insulin much more High Quality, absolutely identical to human insulin on a scale sufficient to provide every patient with insulin and at a much lower cost.
Now hundreds of diseases are known, in which the mechanisms of biochemical disorders have been studied in sufficient detail. In some cases modern methods microanalyzes make it possible to detect such biochemical disorders even in individual cells, and this, in turn, makes it possible to diagnose the presence of such diseases in an unborn child by individual cells in the amniotic fluid.
Knowledge of human genetics makes it possible to predict the probability of the birth of children suffering from hereditary ailments, when one or both spouses are sick or both parents are healthy, but the hereditary disease occurred in the ancestors of the spouses. In some cases, it is possible to predict the probability of having a second healthy child if the first one was affected by a hereditary disease.
As the biological and especially genetic education of the general population increases, married couples who do not yet have children are increasingly turning to geneticists with a question about the risk of having a child affected by a hereditary anomaly.
Medical genetic consultations are now open in many regions and regional centers of our country. The widespread use of medical genetic counseling will play an important role in reducing the frequency of hereditary ailments and save many families from the misfortune of having unhealthy children.
Currently, in many countries, the method of amniocentesis is widely used, which allows the analysis of embryonic cells from the amniotic fluid. Thanks to this method, a woman at an early stage of pregnancy can obtain important information about possible chromosomal or gene mutations in the fetus and avoid the birth of a sick child.

Conclusion
So, the paper outlined the key concepts of genetics, its methods and achievements in recent years. Genetics is a very young science, but the pace of its development is so high that at the moment it occupies the most important place in the system modern sciences, and perhaps major achievements of the last decade of the past century are connected precisely with genetics. Now, at the beginning of the 21st century, prospects are opening up before humanity that fascinate the imagination. Will scientists be able to realize the gigantic potential inherent in genetics in the near future? Will humanity receive the long-awaited deliverance from hereditary diseases, will a person be able to extend his too short life, gain immortality? At present, we have every reason to hope so.
Geneticists predict that by the end of the first decade of the 21st century, genetic vaccines will replace the usual vaccinations, and doctors will have the opportunity to permanently end such incurable diseases as cancer, Alzheimer's disease, diabetes, and asthma. This area already has its own name - gene therapy. She was born just five years ago. But soon it may lose its relevance due to gene diagnostics. According to some forecasts, exceptionally healthy children will be born around 2020: already at the embryonic stage of fetal development, geneticists will be able to correct hereditary problems. Scientists predict that in 2050 there will be attempts to improve the human species. By this time, they will have learned to design people of a certain specialization: mathematicians, physicists, artists, poets, and maybe geniuses.
And closer to the end of the century, the dream of man will finally come true: the aging process, of course, can be controlled, and there it is not far from immortality.
Bibliography:
1. N. Grinn, Biology, Moscow, "MIR", 1993.
2. F. Kibernshtern, Genes and genetics. Moscow, "Paragraph", 1995.
3. R.G. Zayats et al., Biology for University Applicants. MN.: graduate School, 1999
4.
5. General biology. Textbook for grades 10-11 of schools with in-depth study of biology. Under the editorship of Professor A.O. Ruchinsky. Moscow, "Enlightenment" 1993.
6. Vladimir Zaselsky, Igor Lalayants - "Spark", No. 10, March 10, 1997
7. Nature. 1999. P.309-312 (Great Britain).
8.

N. Grinn, Biology, Moscow, "MIR", 1993.
F.Kibernshtern, Genes and genetics. Moscow, Paragraph, 1995
R.G. Zayats et al., Biology for University Applicants. Moscow: Higher School, 1999

Heredity and genes, Science and Life, March 1999
M.M. Tikhomirova, Genetic analysis: tutorial. - L .: Publishing house of the Leningrad University, 1990.
M.M. Tikhomirova, Genetic analysis: a textbook. - L .: Publishing house of the Leningrad University, 1990.

General biology. Textbook for grades 10-11 of schools with in-depth study of biology. Under the editorship of Professor A.O. Ruchinsky. Moscow, "Enlightenment" 1993.

Nature. 1999. p.309-312 (UK)
Heredity and genes, Science and Life, March 1999

What is the genetics of modern Russians? Questions about this do not leave the minds of scientists around the world. It is customary to consider Russian Slavs, therefore, first of all, we will consider the genetic characteristics of the Slavs. However, even such a limitation of the topic leaves a lot of room for research - there are several branches of the Slavs, and the very approach to determining who exactly is understood as the Slavs varies.

Who are we talking about?

Usually, studies of the genetics of Russians, primarily Slavs, begin with an attempt to determine what kind of group of people it is. If you check with a scientist specializing in languages, he will answer without hesitation that there are several language groups, and one of them is Slavic. Consequently, all peoples who have been using the languages ​​of this group for communication for a long time can be called Slavs. For them, this language is native.

Some difficulty in defining the Slavs, and therefore, for modern studies of the genetics of Russians, is created by the similarity of peoples using the same language for communication. We are talking not only about anthropological features, but also about the characteristics of culture. This allows us to expand the linguistic term and include a slightly larger variety of communities among the Slavs.

Separation and unification

Some people think that Russians have bad genetics. This position is explained by a variety of reasons - from historical background to bad habits that have long taken root in society. Scientists do not support such a stereotype. Slavic-speaking peoples and all communities living nearby with them have a close genetic connection. In particular, it is precisely for this reason that the Balto-Slavic populations can be safely considered as a whole. Although for the layman the Balts and Slavs seem far from each other, genetic studies confirm the closeness of the peoples.

Based on linguistic studies, the Slavs and the Balts are also the closest to each other, which makes it possible to single out the corresponding Balto-Slavic group. The geographical feature allows us to say that the genetics of a Russian person has much in common with the Balts. At the same time, it is noted that the eastern and western Slavic branches, although close to each other, have a number of significant differences that do not allow them to be equated with each other. A special case is the southern Slavic branches, whose gene pool is fundamentally different, but quite close to the nationalities with which the Slavic branch is geographically adjacent.

How did it form?

Finding out the origin of Russians in the genetics of the present time is one of the main and most urgent tasks. Scientists involved in this kind of scientific work seek to determine what the ancestral home of the Russian people was, what were the ways of migration of the Slavs, how society developed. In practice, everything is much more complicated than it might seem in the diagram. Even if sequencing complete genome, genetic research cannot give a complete and exhaustive answer to archaeological, linguistic questions. Despite regular research in this direction, it has not yet been possible to determine what the Slavic ancestral home is.

The genetics of Russians and Tatars, as well as other nationalities, has a lot in common. In general, the Slavic gene pool is quite rich in elements obtained from the pre-Slavic population. This is due to historical upheavals. From the side of Novgorod, people gradually moved north and carried their language, culture and religion with them, gradually assimilating the community through which they passed. If the local population was larger in number than the migrating Slavs, the gene pool reflected precisely their features to a greater extent, while the Slavic share had significantly fewer traits.

History and practice

Finding out the genetics of the Russians, scientists found that the Slavic languages ​​spread rapidly, soon covering almost half of the European territory. At the same time, the population was not large enough to inhabit these spaces. Consequently, the scientists suggested, the Slavic gene pool as a whole has pronounced features of some pre-Slavic component, which differs for the south, north and east, west. A similar situation developed with the Indo-European peoples, who spread throughout India and partly in Europe. Genetically, they have few common features, and the explanation was found as follows: the Indo-Europeans assimilated into the European population that originally lived on these lands. From the first came the language, from the second - the gene pool.

Assimilation, revealed in the study of the genetics of Russian scientists, as specialists concluded, is a rule by which many gene pools that exist today are compiled. At the same time, language remains the main ethnic marker. This well illustrates the difference between the Slavs living in the south and north - their genetics differ quite a lot, but the language is the same. Therefore, the people is also one, although it has two different sources that have merged in the process of the development of society. At the same time, attention is drawn to the fact that for the formation of an ethnos, human self-knowledge plays a key role, and it is influenced by language.

Relatives or neighbours?

Many are interested in what is common and different in the genetics of Russians and Tatars. It has long been believed that the period of the Tatar-Mongol yoke had a strong influence on the Russian gene pool, but specific studies conducted relatively recently have shown that the prevailing stereotype is erroneous. There is no unequivocal influence of the Mongol gene pool. But the Tatars turned out to be quite close to the Russians.

In fact, the Tatars are a European people who have a minimum of similarity with the people inhabiting the central Asian regions. This complicates the search for differences between them and Europeans. At the same time, it was established that the Tatar gene pool is close to the Belarusian, Polish, with which historically the people did not have such close contacts as with the Russians. This allows us to talk about the similarities between Russians and Tatars, without explaining it by dominance.

DNA and history

Why in genetics are the northern Russians so different from the southern peoples? Why are west and east so different from each other? Scientists have established that the diversity of ethnic groups is associated with ongoing subtle processes - genetic ones, noticeable only when analyzing long time periods. In order to evaluate genetic changes, it is necessary to study the mitochondrial DNA transmitted from mothers and the Y chromosomes that offspring receive through the father. At the moment, impressive information bases have already been formed, reflecting the sequence in which nucleotides are located in the molecular structure. This allows you to create phylogenetic trees. About two decades ago, a new science was formed, called "molecular anthropology". It examines mtDNA and male specific chromosomes and reveals what the genetic ethnic history is. Research in this area from year to year is becoming more extensive, their number is growing.

In order to reveal all the features of Russians, geneticists are trying to restore the processes under the influence of which the gene pools were formed. It is necessary to evaluate the distribution in space and time of the ethnic group - on the basis of this, more data can be collected on changes in the structure of DNA. The study of phylogeographic variability and DNA has already made it possible to analyze data collected from many thousands of people from different regions of the world. The data are large enough for statistical analyzes to be reliable. Monophyletic groups have been discovered, on the basis of which the evolutionary steps of Russians are gradually restored.

Step by step

By studying the genetics of Russians, scientists were able to identify mitochondrial lines characteristic of peoples living in the eastern and western Eurasian regions. Similar studies were carried out with respect to American, Australian and African ethnic groups. The Eurasian subgroups are believed to have descended from three major macrogroups that formed about 65,000 years ago from a single mtDNA group that originated in Africa.

Analyzing the division of mtDNA in the Eurasian gene pool, it was found that ethno-racial specificity is quite significant, therefore, east and west have cardinal differences. But in the north, monomitochondrial lines are predominantly found. This is especially pronounced in the regional populations. Genetic studies make it possible to determine that only Caucasoid mtDNA or those obtained from the Mongolian race are characteristic of local peoples. The main part of our country, in turn, is the territory of contact, where it has become a source of racial genesis for a long time.

One of the big scientific works, dedicated to the genetics of the Russian people, started about two decades ago and is based on the study of the difference in DNA lines transmitted through the father and mother. To determine how large the variability is within a single population, it was decided to resort to a combined study, simultaneously analyzing polymorphism and individual regions responsible for encrypting information. At the same time, scientists took into account the variability of nucleotide sequences and hypervariable elements that are not responsible for encoding data. It has been established that the mitochondrial genetic fund of the original population of our country is diverse, although certain common groups were still found - they coincided with others common among Europeans. The admixture of the Mongoloid gene pool is estimated at an average of 1.5%, and these are mainly East Eurasian mtDNA.

Revealing the features of the genetics of the Russian people, scientists have attempted to explain why mtDNA shows such diversity, to what extent the phenomenon is associated with the formation of an ethnic group. For this, mtDNA haplotypes of different populations of the European population were analyzed. Phylogeographic studies have shown that there are some common features, but markers are usually combined with rare subgroups and haplotypes. This suggests the existence of some common substrate, which became the basis for the formation of the genetic fund of the Slavs from the eastern, western regions, as well as nationalities living nearby. But the populations of the southern Slavs differ significantly from the Italians and Greeks living nearby.

As part of the assessment of the evolution of Russians in genetics, attempts were made to explain the division of the Slavs into several branches, as well as to track the processes of changing genetic material against this background. Studies have confirmed that there are differences between different groups of Slavs both in the gene pool and anthropological. The variability of the phenomenon is determined by the tightness of contacts with the pre-Slavic population in a particular area, as well as the intensity of mutual influence on neighboring peoples.

How it all began?

Research into the genetics of Russians conducted by modern specialists, as well as the study of the gene pool of other ethnic groups, became possible due to the contribution of great scientists involved in biology, anthropology and human evolution. The contribution to this field of two scientists born in imperial Russia - Mechnikov, Pavlov is considered exceptionally significant. For their merits, they were awarded the Nobel Prize, and in addition, they were able to draw the attention of the general public to biology. Before the First World War, a genetics course began to be taught at a university in St. Petersburg for the first time. In 1917, the Institute of Experimental Biology was opened in Moscow. Three years later, a eugenic society was formed.

It is impossible to overestimate the contribution of Russian scientists to the development of genetics. Koltsov and Bunak, for example, actively studied the frequency of occurrence different groups blood, and their work interested prominent experts of that time. Soon IEB became an object of attraction for the most prominent Russian scientists. When enumerating the list of Russian geneticists, it is reasonable to start with Mechnikov and Pavlov, but do not forget about the following prominent figures:

• Serebrovsky;
• Dubinin;
• Timofeev-Resovsky.

It is worth noting that it was Serebrovsky who became the author of the term "genogeography", which is used to denote a science whose area of ​​interest is the gene pools of human populations.

Science: only forward!

It was at this time, when the most famous Russian geneticists were active, that the word "gene pool" began to be widely used in specific circles. It was introduced to refer to the gene pool inherent in a certain population. Genogeography is gradually turning into a significant tool. The one that is necessary to assess the ethnogenesis of the peoples that exist on our planet. Serebrovsky, by the way, was of the opinion that his offspring is only a part of history, allowing through the gene pool to restore migrations in the past, the processes of mixing ethnic groups and races.

Unfortunately, the study of genetics (Jews, Russians, Tatars, Germans and other ethnic groups) slowed down significantly during the period of "Lysenkoism". At that time, Fisher's work on genetic diversity and natural selection was published in Great Britain. It was he who became the basis for science, relevant for modern scientists. For population genetics. But in the Stalinist Soviet Union, genetics turns out to be the object of persecution at the initiative of Lysenko. It was his ideas that led to the fact that Vavilov died in custody in 1943.

History and science

Shortly after Khrushchev left power, genetics in the USSR began to develop again. In 1966, the Vavilov Institute was opened, where Rychkov's laboratory is actively functioning. In the next decade, significant works were organized with the participation of Cavalli - Sforza, Lewontin. In 1953, it was possible to decipher the structure of DNA - this was a real breakthrough. The authors of the works were awarded Nobel Prize. Geneticists around the world have new tools at their disposal - markers and haplogroups.

As mentioned above, the offspring receive DNA from both parents. Genes are not completely transmitted, but in the process of recombination, individual fragments are observed in different generations. There is a substitution, mixing, the formation of new sequences. Exceptional entities are the above mentioned paternal and maternal specific chromosomes.

Geneticists began to study uniparental markers, and soon it turned out that this is how you can extract a huge amount of information about the processes that took place in the past. Through mtDNA, passed unchanged between generations from the mother, it is possible to trace ancestors that existed tens of millennia ago. Small mutations occur in mtDNA (this is inevitable), and they are also inherited, thanks to which it is possible to track how and why, when the genetic differences characteristic of different ethnic groups formed. 1963 - the year of discovery of mtDNA; 1987 is the year when the work on mtDNA came out, explaining what the common female group of ancestors of all people was.

Who and when?

Initially, scientists assumed that a common group of female progenitors existed in eastern African regions. The period of their existence, according to rough estimates, is 150-250 thousand years ago. Clarification of the past through the mechanisms of genetics made it possible to find out that the period is much closer - about 100-150 millennia have passed since that moment.

In those days, the total number of representatives of the population was relatively small - only a few tens of thousands of individuals, divided into separate groups. Each of them went their own way. About 70-100 thousand years ago, modern man crossed the Bab-el-Mandeb Strait, leaving Africa behind, and began to explore new territories. An alternative variant of migration considered by scientists is through the Sinai Peninsula.

Through mtDNA, scientists got an idea of ​​how the female half of humanity spread around the planet. However, there appeared new information about mutations in the male chromosome. Based on the information collected over several years, at the end of the last century they compiled haplogroups and formed a single tree from them.

Genetics: reality and science

The main task of geneticists was to identify the historical ways of moving people, to determine the links between ethnic groups, as well as the features of evolution. From this point of view, the inhabitants of the Eastern European region are of particular interest. For the first time for such an object of study, uniparental markers began to be studied in the last decade of the last century. The degree of kinship with the Mongoloid race and genetic affinity with the Eastern European peoples were ascertained.

In recent decades, the contribution made to science by Balanovskaya and Balanovsky is considered to be the most significant. Research is being carried out under the leadership of Malyarchuk - they are devoted to the features of the genetic fund of the population of Siberia and the Far Eastern regions. As practice has shown, the maximum benefit can be extracted by examining the population of small settlements - villages and towns. For study, such people are selected whose closest ancestors (second generation) of the same ethnicity are included in the same regional population. However, in some cases, the population of large cities is studied, if this is allowed by conditions and terms of reference project.

It was possible to reveal that certain groups of Russians have quite strong differences in the gene pool. Several dozen varieties of genetic sets have already been studied. The maximum information was collected about people living in the territory of the former kingdom ruled by Ivan the Terrible.

The task of a modern geneticist is to study the characteristics of a particular population, not the people as a whole. Genes have no ethnic identity, they cannot speak. Scientists determine whether the boundaries of the distribution of the genotype coincide with ethnic and linguistic ones, and also determine the specific typical set of genes characteristic of a certain nationality.

Description

Currently, one of the fastest growing areas in medicine is medical genetics. This phenomenon is largely due to the avalanche of discoveries in the field of cellular and molecular biology that occurred at the turn of the 20th - 21st centuries.

The main achievement in this area is the successful completion of the international research project "Human Genome", which opened the way for the practical application of knowledge about the genetic information of our genome for practical use in medicine. In addition to the gigantic amounts of information obtained about the human genome and the laws of its functioning, a technological breakthrough has made it possible to create technologies for determining nucleotide sequences that allow you to quickly extract the necessary information from the genome.

The main role of medical genetics is to identify the hereditary component of the pathogenesis of human diseases, determine the predisposition to the development of a certain range of multifactorial diseases and their timely diagnosis. The influence of genetic factors is described for diseases of two main levels: hereditary diseases, which can include chromosomal and gene diseases; and multifactorial diseases, which include most of the most common human diseases.

Chromosomal diseases

They are caused by disturbances at the level of numerical and structural aberrations of chromosomes - gigantic structures of the cell nucleus, the main task of which is the complex multi-level packaging of DNA - the main carrier of genetic information. The occurrence of chromosomal aberrations, as a rule, occurs during the maturation of gametes and leads to the death of the embryo in the early stages of development. If they persist, they are inherited quite rarely, in 4-5% of cases. This group includes Down, Patau, Edwards, Shereshevsky-Turner, Klinefelter syndromes caused by a violation of the number of chromosomes, and multiple (more than 700 described nosological forms) diseases caused by violations of the structure of chromosomes - deletions, duplications and inversions.

Genetic diseases

They are caused by mutations in structural genes that carry out their function through the synthesis of polypeptides - proteins. Also, such diseases are called monogenic, since the primary sequence of only one of the 22,000 - 24,000 functional genes present in our genome is disturbed. This mainly includes metabolic diseases. Some of them are associated with disorders of amino acid metabolism - phenylketonuria, albinism, alkaptonuria. Others are associated with metabolic disorders of carbohydrates (galactosemia), lipids (Niemann-Pick and Gaucher syndromes), nitrogenous bases (gout, Lesch-Nyhan syndrome), metals (Wilson-Konovalov's disease). Exchange disorders connective tissue cause Marfan's syndrome and fibrodysplasia, and malabsorption in the digestive tract causes cystic fibrosis and lactose intolerance. Often, as a result of a change or loss of the function of one gene, the normal functioning of the entire metabolic system is disrupted, which leads to irreversible pathological conditions. There are monogenic forms of hypertension, Alzheimer's and Parkinson's diseases, epilepsy, immunodeficiencies and various oncological diseases. As a rule, the development of these diseases is strictly determined by a gene mutation, and factors environment do not have a significant effect on their course. Despite the clear progress in determining the nature of gene diseases, their therapy is very difficult.

Multifactorial diseases

They are caused by the combined action of hereditary genetic factors and adverse environmental factors, which together form a predisposition to the disease. The vast majority of human chronic diseases, including inflammation, cardiovascular, endocrine, oncological, etc., are multifactorial diseases. In most cases, the genetic component of multifactorial diseases is not single violations (mutations) of genes, but their polymorphic variants, or alleles, constantly present in the population with a high enough frequency. As a rule (but not always), polymorphic alleles differ by one nucleotide substitution, therefore they are called single nucleotide polymorphisms, or SNPs (from the English. single nucleotide polymorphism). SNPs are located not only in the coding region (exon) of a gene, causing changes in the amino acid composition of the protein product it encodes. Very often, SNPs are located in non-coding regions of the genome, mainly in promoter regions, regulating gene expression. The genes themselves, which have several alleles in a population that differ in their influence on the development of specific diseases, are called predisposition genes or candidate genes. The presence of SNP in them does not inhibit their function, but changes (in any direction) their expression, or shifts the activity of the corresponding protein (enzyme).

Due to the fact that each cell of the human body contains a double set of genetic material, two different alleles of one candidate gene can be in three states: normal homozygous (two normal alleles), heterozygous (one allele is normal, or "wild type", the second pathological , carries the SNP), and a pathological homozygote (two pathological alleles). In various situations, the adverse effect of SNP in the pathological allele can manifest itself in both pathological homozygous and heterozygous forms. In the vast majority of cases, the presence of one unfavorable allele does not lead to the development of the disease. To start the pathological process, the combined action of several mutant alleles, usually homozygous, and unfavorable environmental factors is necessary.

At present, for each multifactorial disease, a fairly wide range of genes has been identified that are involved in the formation of a joint influence on the functioning of a certain metabolic system responsible for the vital activity of one of the body systems. These genes constitute a specific "gene network", and the number of genes participating in such a network for each disease is constantly increasing. In total, about 150 million different SNPs are now known in the human genome, of which about one million can potentially affect the functioning of genes. In fact, not enough a large number of SNPs can have a real impact on the development of disease susceptibility. Therefore, it is the compilation of a real "gene network", the identification of central genes and polymorphisms in it, the study of the interactions of hereditary and environmental factors that is the main task of this section of medical genetics. Based on this knowledge, a complex of preventive and therapeutic measures is developed individually for each patient, taking into account his unique genotype. This is the strategic basis of a new, rapidly developing direction, called predictive (predictive) medicine.

Now more and more facts are accumulating about a significant, and perhaps even a leading role in the formation of a hereditary predisposition of epigenetic variability. Most polymorphisms are variants of the norm, and the influence of each specific SNP on the development of the disease must be considered as a whole. When analyzing each case, it is necessary to take into account the maximum number of hereditary factors (SNPs), compare them with allele frequencies in different samples of people, and be sure to take into account the influence of external factors.

Another direction in the development of medical genetics, based on the analysis of the individual human genome, is pharmacogenetics. Here, the influence of individual characteristics of the organism on the metabolism of drugs is investigated. A fairly large number are now known medicines, for which a different biochemical manifestation is described depending on the patient's genotype. It is worth mentioning suxamethonium, sulfonamides, chlorthiazide, tolbutamide, warfarin, amphetamines, beta-blockers, etc. Development various schemes treatment of diseases, taking into account the genetic status of the patient to minimize side effects and enhancing the therapeutic effect of the drug - modern possibilities of genetic typing of genes involved in the metabolism and detoxification of the body.

Thanks to progress in medical genetics, it is now becoming quite affordable for each patient to receive a genetic passport, a set of information about the variable loci of the genotype. The main direction here is the study of as many polymorphisms as possible, while carefully assessing their individual influence and adding genetic data to the overall picture of the development of a multifactorial disease. Taking advantage of the invariability of genetic information throughout life (with the exception of rare somatic mutations), such a genetic passport can be constantly expanded, new potential genes and loci can be explored, optimizing the strategy and tactics of treating each patient.

The content of the article

GENETICS, a science that studies heredity and variability - properties inherent in all living organisms. The infinite variety of species of plants, animals and microorganisms is maintained by the fact that each species retains its characteristic features over generations: in the cold North and in hot countries, a cow always gives birth to a calf, a chicken breeds chickens, and wheat reproduces wheat. At the same time, living beings are individual: all people are different, all cats are somewhat different from each other, and even spikelets of wheat, if you look at them more closely, have their own characteristics. These two most important properties of living beings - to be similar to their parents and to differ from them - are the essence of the concepts of "heredity" and "variability".

Origins of genetics

The origins of genetics, like any other science, should be sought in practice. Since people started breeding animals and plants, they began to understand that the characteristics of offspring depend on the properties of their parents. By selecting and crossing the best individuals, man from generation to generation created animal breeds and plant varieties with improved properties. The rapid development of breeding and crop production in the second half of the 19th century. gave rise to increased interest in the analysis of the phenomenon of heredity. At that time, it was believed that the material substrate of heredity is a homogeneous substance, and the hereditary substances of parental forms are mixed in the offspring, just as mutually soluble liquids are mixed with each other. It was also believed that in animals and humans, the substance of heredity is somehow connected with blood: the expressions “half-breed”, “purebred”, etc. have survived to this day.

It is not surprising that contemporaries did not pay attention to the results of the work of the abbot of the monastery in Brno Gregor Mendel on crossing peas. None of those who listened to Mendel's report at a meeting of the Society of Naturalists and Physicians in 1865 was able to unravel the fundamental biological laws in some "strange" quantitative relationships discovered by Mendel in the analysis of pea hybrids, and in the person who discovered them, the founder of a new science - genetics. After 35 years of oblivion, Mendel's work was appreciated: his laws were rediscovered in 1900, and his name entered the history of science.

Laws of genetics

The laws of genetics, discovered by Mendel, Morgan and a galaxy of their followers, describe the transmission of traits from parents to children. They argue that all inherited traits are determined by genes. Each gene can be represented in one or more forms called alleles. All cells of the body, except for sex cells, contain two alleles of each gene, i.e. are diploid. If two alleles are identical, the organism is said to be homozygous for that gene. If the alleles are different, the organism is said to be heterozygous. Cells involved in sexual reproduction (gametes) contain only one allele of each gene, i.e. they are haploid. Half of the gametes produced by an individual carry one allele, and half carry the other. The union of two haploid gametes during fertilization leads to the formation of a diploid zygote, which develops into an adult organism.

Genes are certain pieces of DNA; they are organized into chromosomes located in the nucleus of the cell. Each type of plant or animal has a certain number of chromosomes. In diploid organisms, the number of chromosomes is paired, two chromosomes of each pair are called homologous. Let's say a person has 23 pairs of chromosomes, with one homologue of each chromosome coming from the mother and the other from the father. There are also extranuclear genes (in mitochondria, and in plants - also in chloroplasts).

Features of the transmission of hereditary information are determined by intracellular processes: mitosis and meiosis. Mitosis is the process of distributing chromosomes to daughter cells during cell division. As a result of mitosis, each chromosome of the parent cell is duplicated and identical copies diverge to the daughter cells; in this case, hereditary information is completely transmitted from one cell to two daughter cells. This is how cell division occurs in ontogenesis, i.e. the process of individual development. Meiosis is a specific form of cell division that occurs only during the formation of sex cells, or gametes (sperm and eggs). Unlike mitosis, the number of chromosomes during meiosis is halved; only one of the two homologous chromosomes of each pair gets into each daughter cell, so that in half of the daughter cells there is one homologue, in the other half - the other; while chromosomes are distributed in gametes independently of each other. (The genes of mitochondria and chloroplasts do not follow the law of equal distribution during division.) When two haploid gametes merge (fertilization), the number of chromosomes is restored again - a diploid zygote is formed, which received a single set of chromosomes from each parent.

Methodical approaches.

Thanks to what features of the methodical approach was Mendel able to make his discoveries? For his experiments on crossing, he chose pea lines that differ in one alternative trait (seeds are smooth or wrinkled, cotyledons are yellow or green, the shape of the bean is convex or constricted, etc.). He analyzed the offspring from each crossing quantitatively, i.e. counted the number of plants with these traits, which no one had done before him. Thanks to this approach (the choice of qualitatively different traits), which formed the basis of all subsequent genetic research, Mendel showed that the traits of the parents do not mix in the offspring, but are transmitted unchanged from generation to generation.

Mendel's merit also lies in the fact that he put into the hands of geneticists a powerful method for studying hereditary traits - hybridological analysis, i.e. a method of studying genes by analyzing the traits of descendants from certain crosses. The laws of Mendel and hybridological analysis are based on events that occur in meiosis: alternative alleles are in the homologous chromosomes of hybrids and therefore diverge equally. It is the hybridological analysis that determines the requirements for the objects of general genetic research: these should be easily cultivated organisms that give numerous offspring and have a short reproductive period. Such requirements among higher organisms are met by the fruit fly Drosophila - Drosophila melanogaster. For many years it became a favorite object of genetic research. Through the efforts of geneticists different countries fundamental genetic phenomena were discovered on it. It was found that the genes are located linearly in the chromosomes and their distribution in the offspring depends on the processes of meiosis; that genes located on the same chromosome are inherited together (gene linkage) and are subject to recombination (crossing over). Genes localized in the sex chromosomes have been discovered, the nature of their inheritance has been established, and the genetic basis for determining sex has been revealed. It has also been found that genes are not immutable but subject to mutations; that a gene is a complex structure and there are many forms (alleles) of the same gene.

Then, microorganisms became the object of more scrupulous genetic research, on which they began to study the molecular mechanisms of heredity. Yes, on Escherichia coli Escherichia coli the phenomenon of bacterial transformation was discovered - the inclusion of DNA belonging to the donor cell into the recipient cell - and for the first time it was proved that it is DNA that is the carrier of genes. The structure of DNA was discovered, the genetic code was deciphered, the molecular mechanisms of mutations, recombination, genomic rearrangements were identified, the regulation of gene activity, the phenomenon of movement of genome elements, etc. were studied. ( cm. CELL; HEREDITY; MOLECULAR BIOLOGY) . Along with the indicated model organisms, genetic studies were carried out on many other species, and the universality of the main genetic mechanisms and methods for their study was shown for all organisms, from viruses to humans.

Achievements and problems of modern genetics.

On the basis of genetic research, new areas of knowledge (molecular biology, molecular genetics), relevant biotechnologies (such as genetic engineering) and methods (for example, polymerase chain reaction) have arisen that make it possible to isolate and synthesize nucleotide sequences, integrate them into the genome, and obtain hybrid DNA with properties that do not exist in nature. Many drugs have been obtained, without which medicine is already unthinkable ( cm. GENETIC ENGINEERING) . The principles of breeding transgenic plants and animals with characteristics of different species have been developed. It became possible to characterize individuals by many polymorphic DNA markers: microsatellites, nucleotide sequences, etc. Most molecular biological methods do not require hybridological analysis. However, in the study of traits, analysis of markers and mapping of genes, this classical method of genetics is still needed.

Like any other science, genetics has been and remains the weapon of unscrupulous scientists and politicians. Such a branch of it as eugenics, according to which the development of a person is completely determined by his genotype, served as the basis for the creation of racial theories and sterilization programs in the 1930s-1960s. On the contrary, the denial of the role of genes and the acceptance of the idea of ​​the dominant role of the environment led to the cessation of genetic research in the USSR from the late 1940s to the mid-1960s. Now there are ecological and ethical problems in connection with the work on the creation of "chimeras" - transgenic plants and animals, "copying" animals by transplanting the cell nucleus into a fertilized egg, genetic "certification" of people, etc. In the leading powers of the world, laws are being passed that aim to prevent the undesirable consequences of such work.

Modern genetics has provided new opportunities for studying the activity of an organism: with the help of induced mutations, it is possible to turn off and on almost any physiological process, interrupt the biosynthesis of proteins in the cell, change morphogenesis, and stop development at a certain stage. We can now delve deeper into population and evolutionary processes ( cm. POPULATION GENETICS), to study hereditary diseases ( cm. GENETIC COUNSELING), a problem cancer and much more. In recent years, the rapid development of molecular biological approaches and methods has allowed geneticists not only to decipher the genomes of many organisms, but also to design living beings with desired properties. Thus, genetics opens up ways to model biological processes and contributes to the fact that biology, after a long period of fragmentation into separate disciplines, enters an era of unification and synthesis of knowledge.