Genetics research method based on study. Genetic research methods

Municipal educational institution

secondary school №37

Human genetic research methods

Smolensk 2010

Introduction

1 genetics as a science

1.1 The main stages in the development of genetics

1.2 The main tasks of genetics

1.3 The main sections of genetics

1.4 The influence of genetics on other branches of biology

2.Human genetics (anthropogenetics)

3. Methods for the study of heredity

3.1 Genealogical method

3.2 Twin method

3.3 Cytogenetic (karyotypic) methods

3.4 Biochemical methods

3.5 Population methods

Conclusion

Literature

Application

Introduction

If the 19th century rightfully entered the history of world civilization as the Age of Physics, then the rapidly ending 20th century, in which we were lucky to live, in all likelihood, has prepared a place for the Age of Biology, and perhaps the Age of Genetics.

Indeed, in less than 100 years after the second discovery of Mendel's laws, genetics traveled a triumphant path from the naturalphilos understanding of the laws of heredity and variability through the experimental accumulation of the facts of formal genetics to the molecular biological understanding of the essence of the gene, its structure and function. From theoretical constructions about a gene as an abstract unit of heredity to understanding its material nature as a fragment of a DNA molecule encoding the amino acid structure of a protein, to cloning individual genes, creating detailed genetic maps of humans and animals, identifying genes whose mutations are associated with hereditary ailments, developing biotechnology methods, and genetic engineering, allowing targeted production of organisms with given hereditary characteristics, as well as targeted correction of human mutant genes, i.e. gene therapy for hereditary diseases. Molecular genetics has significantly deepened our understanding of the essence of life, the evolution of living nature, structural and functional mechanisms of regulation of individual development. Thanks to her successes, the solution to the global problems of mankind related to the protection of its gene pool has begun.

The middle and second half of the twentieth century was marked by a significant decrease in the frequency and even complete elimination of a number of infectious diseases, a decrease in infant mortality, and an increase in life expectancy. In the developed countries of the world, the focus of health services has been shifted to the fight against chronic human pathology, diseases of the cardiovascular system, and oncological diseases.

Goals and objectives of my abstract:

· Consider the main stages of development, tasks and goals of genetics;

· Give a precise definition of the term "human genetics" and consider the essence of this type of genetics;

· Consider methods for studying human heredity.

1. Genetics as a science

1 The main stages of the development of genetics

The origins of genetics, like any science, should be sought in practice. Genetics arose in connection with the breeding of domestic animals and the cultivation of plants, as well as with the development of medicine. Ever since man began to use the crossing of animals and plants, he was faced with the fact that the properties and characteristics of the offspring depend on the properties of the parent individuals chosen for crossing. Selecting and crossing the best descendants, a person from generation to generation created related groups - lines, and then breeds and varieties with characteristic hereditary properties.

Although these observations and comparisons could not yet become the basis for the formation of science, the rapid development of animal husbandry and breeding, as well as plant growing and seed production in the second half of the 19th century gave rise to an increased interest in the analysis of the phenomenon of heredity.

The development of the science of heredity and variability was especially strongly promoted by Charles Darwin's doctrine of the origin of species, which introduced into biology the historical method of studying the evolution of organisms. Darwin himself made a lot of efforts to study heredity and variability. He collected a huge number of facts, made on their basis a number of correct conclusions, but he was unable to establish the laws of heredity.

His contemporaries, the so-called hybridizers, crossing various forms and looking for the degree of similarity and difference between parents and descendants, also failed to establish general patterns of inheritance.

Another condition that contributed to the formation of genetics as a science was advances in the study of the structure and behavior of somatic and germ cells. Back in the 70s of the last century, a number of cytologists (Chistyakov in 1972, Strasburger in 1875) discovered an indirect division of a somatic cell called karyokinesis (Schleicher in 1878) or mitosis (Flemming in 1882) ... Permanent elements of the cell nucleus in 1888 at the suggestion of Valdeir were called "chromosomes". In those same years, Flemming divided the entire cycle of cell division into four main phases: prophase, metaphase, anaphase and telophase.

Simultaneously with the study of the mitosis of the somatic cell, there was a study of the development of germ cells and the mechanism of fertilization in animals and plants. O. Hertwig in 1876 for the first time in echinoderms establishes the fusion of the nucleus of the sperm with the nucleus of the egg. N.N. Gorozhankin in 1880 and E. Strasburger in 1884 establish the same for plants: the first for gymnosperms, the second for angiosperms.

In the same Van Beneden (1883) and others, the cardinal fact is clarified that in the process of development, germ cells, unlike somatic ones, undergo a reduction in the number of chromosomes exactly by half, and during fertilization - the fusion of the female and male nuclei - the normal number of chromosomes is restored constant for each species. Thus, it was shown that each species is characterized by a certain number of chromosomes.

So, the listed conditions contributed to the emergence of genetics as a separate biological discipline - a discipline with its own subject and research methods.

The official birth of genetics is considered to be the spring of 1900, when three botanists, independently of each other, in three different countries, at different sites, came to the discovery of some of the most important patterns of inheritance of traits in the offspring of hybrids. G. de Vries (Holland), on the basis of work with evening primrose, poppy, dope and other plants, reported "the law of splitting hybrids"; K. Correns (Germany) established the laws of splitting on corn and published the article "Gregor Mendel's Law on the Behavior of the Offspring in Race Hybrids"; in the same year K. Cermak (Austria) appeared in print with an article (On artificial crossing in Pisum Sativum).

Science knows almost no unexpected discoveries. The most brilliant discoveries that create stages in its development almost always have their predecessors. So it happened with the discovery of the laws of heredity. It turned out that three botanists, who discovered the pattern of splitting of intraspecific hybrids in the offspring, only "rediscovered" the patterns of inheritance, discovered back in 1865 by Gregor Mendel and described by him in the article "Experiments on Plant Hybrids" published in the "Proceedings" of the Society of Naturalists in Brunne (Czechoslovakia).

G. Mendel on pea plants developed methods of genetic analysis of the inheritance of individual traits of an organism and established two fundamentally important phenomena:

Signs are determined by individual hereditary factors that are transmitted through the germ cells;

Individual signs of organisms do not disappear during crossing, but remain in the offspring in the same form in which they were in the parental organisms.

For the theory of evolution, these principles were of fundamental importance. They revealed one of the most important sources of variability, namely, the mechanism for maintaining the fitness of the characteristics of a species in a number of generations. If the adaptive characteristics of organisms, which arose under the control of selection, were absorbed, disappeared during crossing, then the progress of the species would be impossible.

All subsequent development of genetics was associated with the study and expansion of these principles and their application to the theory of evolution and selection.

A number of problems logically follow from the established principles of Mendel, which receive their solution step by step as genetics develops. In 1901, de Vries formulates the theory of mutations, which states that the hereditary properties and characteristics of organisms change in leaps and bounds - mutationally.

In 1903, the Danish plant physiologist V. Johannsen published his work "On inheritance in populations and pure lines", in which it was experimentally established that externally similar plants belonging to the same variety are hereditarily different - they constitute a population. The population consists of hereditarily different individuals or related groups - lines. In the same study, the existence of two types of variability of organisms is most clearly established: hereditary, determined by genes, and non-hereditary, determined by a random combination of factors acting on the manifestation of traits.

At the next stage in the development of genetics, it was proved that hereditary forms are associated with chromosomes. The first fact revealing the role of chromosomes in heredity was the proof of the role of chromosomes in determining sex in animals and the discovery of a 1: 1 sex cleavage mechanism.

Since 1911, T. Morgan and his colleagues at Columbia University in the USA began to publish a series of works in which he formulated the chromosomal theory of heredity. Experimentally proving that the main carriers of genes are chromosomes, and that genes are located linearly in chromosomes.

In 1922 N.I. Vavilov formulates the law of homologous series in hereditary variation, according to which species of plants and animals related in origin have similar series of hereditary variation.

Applying this law, N.I. Vavilov established centers of origin of cultivated plants, in which the greatest diversity of hereditary forms is concentrated.

In 1925 in our country G.A. Nadson and G.S. Filippov on mushrooms, and in 1927 G. Möller in the USA on the fruit fly Drosophila obtained proof of the influence of X-rays on the occurrence of hereditary changes. At the same time, it was shown that the rate of occurrence of mutations increases more than 100 times. These studies proved the variability of genes under the influence of environmental factors. Proof of the influence of ionizing radiation on the occurrence of mutations led to the creation of a new branch of genetics - radiation genetics, the importance of which has grown even more with the discovery of atomic energy.

In 1934, T. Pinter on giant chromosomes of the dipteran salivary glands proved that the discontinuity of the morphological structure of chromosomes, expressed in the form of various disks, corresponds to the arrangement of genes in chromosomes previously established by purely genetic methods. This discovery laid the foundation for the study of the structure and functioning of the gene in the cell.

In the period from the 40s to the present, a number of discoveries (mainly on microorganisms) of completely new genetic phenomena have been made, which have revealed the possibilities of analyzing the structure of a gene at the molecular level. In recent years, with the introduction of new research methods into genetics, borrowed from microbiology, we have come to a clue of how genes control the sequence of amino acids in a protein molecule.

First of all, it should be said that it has now been fully proven that the carriers of heredity are chromosomes, which consist of a bundle of DNA molecules.

Quite simple experiments were carried out: pure DNA was isolated from killed bacteria of one strain with a special external characteristic and transferred to living bacteria of another strain, after which the multiplying bacteria of the latter acquired the characteristic of the first strain. Numerous similar experiments show that it is DNA that is the carrier of heredity.

In 1953 F. Crick (England) and J. Watston (USA) deciphered the structure of the DNA molecule. They found that each DNA molecule is composed of two polydeoxyribonucleic chains, spirally twisted around a common axis.

At present, approaches have been found to solve the problem of the organization of the hereditary code and its experimental decoding. Genetics, together with biochemistry and biophysics, came close to elucidating the process of protein synthesis in a cell and the artificial synthesis of a protein molecule. This begins a completely new stage in the development of not only genetics, but biology as a whole.

The development of genetics to the present day is a continuously expanding body of research on the functional, morphological and biochemical discreteness of chromosomes. A lot has already been done in this area, a lot has already been done, and every day the cutting edge of science is approaching the goal of unraveling the nature of the gene. To date, a number of phenomena have been established that characterize the nature of the gene. First, a gene in a chromosome has the property of self-reproduction (autoreproduction); secondly, it is capable of mutational change; third, it is associated with a specific chemical structure of deoxyribonucleic acid - DNA; fourth, it controls the synthesis of amino acids and their sequences into a protein molecule. In connection with the latest research, a new understanding of the gene as a functional system is being formed, and the effect of a gene on the determination of traits is considered in an integral system of genes - the genotype.

The unfolding prospects for the synthesis of living matter attract great attention of geneticists, biochemists, physicists and other specialists.

1.2 The main tasks of genetics

genetics biology heredity genealogical

Genetic research pursues two goals: the knowledge of the laws of heredity and variability and the search for ways of practical use of these laws. Both are closely related: the solution of practical problems is based on conclusions obtained from the study of fundamental genetic problems and at the same time delivers factual data that are important for expanding and deepening theoretical concepts.

From generation to generation, information is transmitted (although sometimes in a somewhat distorted form) about all the various morphological, physiological and biochemical characteristics that should be realized in descendants. Based on this cybernetic nature of genetic processes, it is convenient to formulate four main theoretical problems studied by genetics:

First, the problem of storing genetic information. It is studied in which material structures of the cell the genetic information is contained and how it is encoded there.

Secondly, the problem of transferring genetic information. The mechanisms and patterns of transmission of genetic information from cell to cell and from generation to generation are being studied.

Third, the problem of the implementation of genetic information. It is studied how genetic information is embodied in specific features of a developing organism, interacting with the influences of the environment, which, to one degree or another, changes these features, sometimes significantly.

Fourth, the problem of changing genetic information. The types, causes and mechanisms of these changes are being studied.

Achievements of genetics are used to select the types of crosses that best affect the genotypic structure (cleavage) in offspring, to select the most effective selection methods, to regulate the development of hereditary traits, control the mutational process, directed changes in the genome of an organism using genetic engineering and site-specific mutagenesis ... Knowing how different methods of selection affect the genotypic structure of the initial population (breed, variety) allows you to use those selection methods that most quickly change this structure in the desired direction. Understanding the ways of realization of genetic information in the course of ontogenesis and the influence exerted on these processes by the environment helps to select conditions that promote the most complete manifestation of valuable traits in a given organism and "suppression" of undesirable ones. This is important for increasing the productivity of domestic animals, cultivated plants and industrial microorganisms, as well as for medicine, as it helps prevent the manifestation of a number of hereditary human diseases.

The study of physical and chemical mutagens and the mechanism of their action makes it possible to artificially obtain many hereditarily modified forms, which contributes to the creation of improved strains of beneficial microorganisms and varieties of cultivated plants. Knowledge of the patterns of the mutation process is necessary for the development of measures to protect the human and animal genome from damage by physical (mainly radiation) and chemical mutagens.

The success of any genetic research is determined not only by the knowledge of the general laws of heredity and variability, but also by the knowledge of the particular genetics of the organisms with which the work is carried out. Although the basic laws of genetics are universal, they have in different organisms and features due to differences, for example, in the biology of reproduction and the structure of the genetic apparatus. In addition, for practical purposes, it is necessary to know which genes are involved in determining the characteristics of a given organism. Therefore, the study of the genetics of specific traits of an organism is an indispensable element of applied research.

3 The main sections of genetics

Modern genetics is represented by many sections of both theoretical and practical interest. Among the sections of general, or "classical" genetics, the main ones are: genetic analysis, the foundations of the chromosomal theory of heredity, cytogenetics, cytoplasmic (extra-nuclear) heredity, mutations, modifications. Molecular genetics, genetics of ontogeny (phenogenetics), population genetics (genetic structure of populations, the role of genetic factors in microevolution), evolutionary genetics (the role of genetic factors in speciation and macroevolution), genetic engineering, genetics of somatic cells, immunogenetics, private genetics - genetics bacteria, virus genetics, animal genetics, plant genetics, human genetics, medical genetics and many others. etc. The newest branch of genetics - genomics - studies the processes of formation and evolution of genomes.

4 The influence of genetics on other branches of biology

Genetics occupies a central place in modern biology, studying the phenomena of heredity and variability, to a greater extent determining all the main properties of living things. The universality of the genetic material and the genetic code underlies the unity of all living things, and the diversity of life forms is the result of the peculiarities of its implementation in the course of the individual and historical development of living beings. Advances in genetics are an important component of almost all modern biological disciplines. The synthetic theory of evolution is the closest combination of Darwinism and genetics. The same can be said about modern biochemistry, the main provisions of which about how the synthesis of the main components of living matter - proteins and nucleic acids - is controlled, are based on the achievements of molecular genetics. Cytology focuses on the structure, reproduction and functioning of chromosomes, plastids and mitochondria, that is, the elements in which genetic information is recorded. The taxonomy of animals, plants, and microorganisms is increasingly making use of the comparison of genes encoding enzymes and other proteins, as well as direct comparison of the nucleotide sequences of chromosomes to establish the degree of relationship between taxa and elucidate their phylogeny. Various physiological processes in plants and animals are studied using genetic models; in particular, in studies of the physiology of the brain and nervous system, they use special genetic methods, lines of Drosophila and laboratory mammals. Modern immunology is entirely based on genetic data on the mechanism of antibody synthesis. Achievements of genetics, to one degree or another, often very significant, are an integral part of virology, microbiology, embryology. We can rightfully say that modern genetics occupies a central place among biological disciplines.

2. Human genetics (anthropogenetics)

1. Methods for studying human heredity: genealogical, twin, cytogenetic, biochemical and population

Genetic diseases and hereditary diseases. The value of medical genetic counseling and prenatal diagnostics. Possibilities of genetic correction of diseases.

Human genetics is a special section of genetics that studies the features of inheritance of traits in humans, hereditary diseases (medical genetics), and the genetic structure of human populations. Human genetics is the theoretical basis of modern medicine and modern healthcare.

It is now firmly established that in the living world the laws of genetics are universal, and they are valid for humans.

However, since a person is not only a biological, but also a social being, human genetics differs from the genetics of most organisms in a number of features: - hybridological analysis (the method of crossing) is not applicable to the study of human inheritance; therefore, specific methods are used for genetic analysis: genealogical (method of analysis of pedigrees), twin, as well as cytogenetic, biochemical, population and some other methods;

a person is characterized by social characteristics that are not found in other organisms, for example, temperament, complex communication systems based on speech, as well as mathematical, visual, musical and other abilities;

thanks to public support, the survival and existence of people with obvious deviations from the norm is possible (in the wild, such organisms are not viable).

Human genetics studies the features of the inheritance of traits in humans, hereditary diseases (medical genetics), the genetic structure of human populations. Human genetics is the theoretical basis of modern medicine and modern healthcare. There are several thousand known genetic diseases, which are almost 100% dependent on the genotype of the individual. The most terrible of them are: acidic fibrosis of the pancreas, phenylketonuria, galactosemia, various forms of cretinism, hemoglobinopathy, as well as Down, Turner, Kleinfelter syndromes. In addition, there are diseases that depend on both the genotype and the environment: coronary artery disease, diabetes mellitus, rheumatoid diseases, stomach and duodenal ulcers, many oncological diseases, schizophrenia and other mental diseases.

The tasks of medical genetics are to timely identify the carriers of these diseases among parents, identify sick children and develop recommendations for their treatment. An important role in the prevention of genetically determined diseases is played by genetic medical consultations and prenatal diagnostics (that is, the detection of diseases at the early stages of the body's development).

There are special sections of applied human genetics (ecological genetics, pharmacogenetics, genetic toxicology) that study the genetic foundations of health care. When developing medicinal products, when studying the body's response to adverse factors, it is necessary to take into account both the individual characteristics of people and the characteristics of human populations.

Let us give examples of the inheritance of some morphophysiological traits.

Dominant and recessive traits in humans

(for some traits, the genes that control them are indicated)

Incomplete dominance (genes that control the trait are indicated) (table # 2, see ave.)

Hair color inheritance (controlled by four genes, polymeric inherited) (table # 3, see page)

3. Methods for studying human heredity

A pedigree is a diagram that reflects the bonds between family members. Analyzing pedigrees, they study any normal or (more often) pathological sign in generations of people who are in family ties.

3.1 Genealogical methods

Genealogical methods are used to determine the hereditary or non-hereditary nature of a trait, dominance or recessiveness, chromosome mapping, sex linkage, and to study the mutational process. As a rule, the genealogical method forms the basis for conclusions in medical genetic counseling.

When compiling pedigrees, standard designations are used. The person (individual) from which the research begins is called the proband (if the pedigree is drawn up in such a way that they descend from the proband to his offspring, then it is called the family tree). A descendant of a married couple is called a sibling, siblings are called siblings, cousins are called cousins siblings, etc. Descendants who have a common mother (but different fathers) are called consanguineous, and descendants who have a common father (but different mothers) are called consanguineous; if the family has children from different marriages, moreover, they do not have common ancestors (for example, a child from a mother's first marriage and a child from a father's first marriage), then they are called half-hearted.

Each member of the pedigree has its own cipher, consisting of a Roman numeral and an Arabic numeral, denoting the generation number and the individual number, respectively, when the generations are numbered sequentially from left to right. The pedigree should have a legend, that is, an explanation of the accepted designations. In closely related marriages, there is a high probability K of detecting the same unfavorable allele or chromosomal aberration in the spouses.

Here are the values of K for some pairs of relatives with monogamy:

K [parent-offspring] = K [sibs] = 1/2;

K [grandfather-grandson] = K [uncle-nephew] = 1/4;

K [cousins sibs] = K [great-grandfather-great-grandson] = 1/8;

K [second cousins] = 1/32;

K [fourth cousins sibs] = 1/128. Usually such distant relatives as part of the same family are not considered.

On the basis of genealogical analysis, a conclusion is made about the hereditary condition of the trait. For example, the inheritance of hemophilia A among the descendants of the English Queen Victoria is traced in detail. Genealogical analysis has shown that hemophilia A is a sex-linked recessive disease.

2 Twin method

Twins are two or more children, conceived and born by the same mother almost simultaneously. The term "twins" is used to refer to humans and those mammals that normally have one baby (calf). Distinguish between identical and fraternal twins.

Identical (monozygous, identical) twins arise at the earliest stages of zygote cleavage, when two or four blastomeres retain the ability to develop into a full-fledged organism during separation. Since the zygote divides by mitosis, the genotypes of identical twins are, at least initially, completely identical. Identical twins are always of the same sex, during the period of intrauterine development they have one placenta.

Fraternal (dizygotic, non-identical) twins arise differently - when two or more simultaneously matured eggs are fertilized. Thus, they share about 50% of the genes in common. In other words, they are similar to ordinary brothers and sisters in their genetic constitution and can be either same-sex or opposite-sex.

Thus, the similarity between identical twins is determined by the same genotypes and the same conditions of intrauterine development. The similarity between fraternal twins is determined only by the same conditions of intrauterine development.

The birth rate of twins in relative numbers is small and is about 1%, of which 1/3 are monozygotic twins. However, in terms of the total population of the Earth, over 30 million fraternal and 15 million identical twins live in the world.

For studies on twins, it is very important to establish the reliability of the zygosity. Most accurately, zygosity is established using reciprocal transplantation of small areas of skin. In dizygotic twins, grafts are always rejected, while in monozygous twins, the transplanted skin pieces are successfully engrafted. Transplanted kidneys, transplanted from one of the monozygotic twins to another, also function successfully and for a long time.

When comparing identical and fraternal twins raised in the same environment, one can draw a conclusion about the role of genes in the development of traits. The conditions of postnatal development for each of the twins may be different. For example, monozygotic twins were separated a few days after birth and were raised under different conditions. Comparing them after 20 years for many external features (height, head volume, number of grooves in fingerprints, etc.) revealed only insignificant differences. At the same time, the environment affects a number of normal and pathological signs.

The twin method allows you to make informed conclusions about the heritability of traits: the role of heredity, environment and random factors in determining certain traits of a person,

Heritability is the contribution of genetic factors to the formation of a trait, expressed in fractions of a unit or percentage.

To calculate the heritability of traits, the degree of similarity or difference in a number of traits is compared in different types of twins.

Let's consider some examples illustrating the similarity (concordance) and the difference (discordance) of many features (table No. 4, see also.)

Attention is drawn to the high degree of similarity of identical twins in such serious diseases as schizophrenia, epilepsy, diabetes mellitus.

In addition to morphological signs, as well as the timbre of the voice, gait, facial expressions, gestures, etc., they study the antigenic structure of blood cells, serum proteins, and the ability to taste certain substances.

Of particular interest is the inheritance of socially significant traits: aggressiveness, altruism, creative, research, organizational abilities. It is believed that socially significant traits are approximately 80% due to the genotype.

3 Cytogenetic (karyotypic) methods

Cytogenetic methods are used primarily in the study of the karyotypes of individual individuals. The human karyotype is fairly well understood, and differential staining can accurately identify all chromosomes. The total number of chromosomes in the haploid set is 23. Of these, 22 chromosomes are the same in both men and women; they are called autosomes. In the diploid set (2n = 46), each autosome is represented by two homologues. The twenty-third chromosome is the sex chromosome, it can be represented by either the X or Y chromosome. The sex chromosomes in women are represented by two X chromosomes, and in men by one X chromosome and one Y chromosome.

A change in karyotype is usually associated with the development of genetic diseases.

By cultivating human cells in vitro, a sufficiently large material for the preparation of preparations can be quickly obtained. For karyotyping, a short-term culture of peripheral blood leukocytes is usually used.

Cytogenetic methods are also used to describe interphase cells. For example, by the presence or absence of sex chromatin (Barr's bodies, which are inactivated X chromosomes), one can not only determine the sex of individuals, but also identify some genetic diseases associated with a change in the number of X chromosomes.

Mapping of human chromosomes.

Biotechnology is widely used to map human genes. In particular, cell engineering techniques make it possible to combine different types of cells. The fusion of cells belonging to different biological species is called somatic hybridization. The essence of somatic hybridization is to obtain synthetic cultures by fusion of protoplasts of various types of organisms. Various physicochemical and biological methods are used for cell fusion. After fusion of protoplasts, multinucleated heterokaryotic cells are formed. Subsequently, during the fusion of nuclei, synkaryotic cells are formed, containing chromosomal sets of different organisms in the nuclei. When such cells divide in vitro, hybrid cell cultures are formed. Currently received and cultivated cell hybrids "man × mouse, man × rat "and many others.

In hybrid cells obtained from different strains of different species, one of the parental genomes gradually loses chromosomes. These processes take place intensively, for example, in cell hybrids between a mouse and a person. If at the same time follow any biochemical marker (for example, a certain human enzyme) and simultaneously carry out cytogenetic control, then, in the end, it is possible to associate the disappearance of the chromosome simultaneously with the biochemical trait. This means that the gene encoding this trait is localized on this chromosome.

Additional information on the localization of genes can be obtained by analyzing chromosomal mutations (deletions).

4 Biochemical methods

The whole variety of biochemical methods is divided into two groups:

a) Methods based on the identification of certain biochemical products due to the action of different alleles. The easiest way to identify alleles is by a change in enzyme activity or by a change in any biochemical trait.

b) Methods based on the direct detection of altered nucleic acids and proteins using gel electrophoresis in combination with other techniques (blot hybridization, autoradiography).

The use of biochemical methods makes it possible to identify heterozygous carriers of diseases. For example, in heterozygous carriers of the phenylketonuria gene, the level of phenylalanine in the blood changes.

Methods of genetics of mutagenesis

The mutation process in humans in humans, as in all other organisms, leads to the emergence of alleles and chromosomal rearrangements that adversely affect health.

Gene mutations. About 1% of newborns become ill due to gene mutations, some of which are newly emerged. The rate of mutation of various genes in the human genotype is not the same. Genes are known that mutate at a frequency of 10-4 per gamete per generation. However, most other genes mutate at a frequency that is hundreds of times lower (10-6). Below are examples of the most common gene mutations in humans (table # 5, see ave.)

Chromosomal and genomic mutations in the absolute majority arise in the germ cells of the parents. One in 150 newborns carries a chromosomal mutation. About 50% of early abortions are due to chromosomal mutations. This is due to the fact that one in 10 human gametes is a carrier of structural mutations. The age of the parents, especially the age of the mothers, plays an important role in the increase in the frequency of chromosomal and possibly gene mutations.

Polyploidy is very rare in humans. There are known cases of the birth of triploids - these newborns die early. Tetraploids are found among aborted fetuses.

At the same time, there are factors that reduce the frequency of mutations - antimutagens. Antimutagens include some antioxidant vitamins (for example, vitamin E, unsaturated fatty acids), sulfur-containing amino acids, as well as various biologically active substances that increase the activity of repair systems.

5 Population methods

The main features of human populations are: the commonality of the territory in which this group of people lives, and the possibility of free marriage. Factors of isolation, that is, limiting the freedom of choice of spouses, a person may have not only geographic, but also religious and social barriers.

In human populations, there is a high level of polymorphism for many genes: that is, the same gene is represented by different alleles, which leads to the existence of several genotypes and corresponding phenotypes. Thus, all members of the population differ from each other genetically: it is practically impossible to find even two genetically identical people in a population (with the exception of identical twins).

Various forms of natural selection operate in human populations. Selection acts both in the prenatal state and in subsequent periods of ontogenesis. The most pronounced stabilizing selection is directed against unfavorable mutations (for example, chromosomal rearrangements). A classic example of heterozygote selection is the spread of sickle cell disease.

Population methods make it possible to estimate the frequencies of the same alleles in different populations. In addition, population methods make it possible to study the mutational process in humans. By the nature of radiosensitivity, the human population is genetically heterogeneous. In some people with genetically determined defects in DNA repair, the radiosensitivity of chromosomes is increased 5 ... 10 times compared to most members of the population.

Conclusion

So, to adequately perceive the revolution in biology and medicine taking place before our eyes, to be able to take advantage of its tempting fruits and avoid temptations that are dangerous for humanity - this is what doctors, biologists, and representatives of other specialties, and simply an educated person need today.

To preserve the gene pool of mankind, in every possible way protecting it from risky interventions, and at the same time to make the most of the invaluable information already received in terms of diagnostics, prevention and treatment of many thousands of hereditary ailments - this is the task that needs to be solved today and with which we will enter a new 21st century.

In my essay, I set the tasks that I needed to consider. I learned more about genetics. I learned what genetics is. Considered its main stages of development, tasks and goals of modern genetics. I also considered one of the varieties of genetics - human genetics. She gave a precise definition of this term and considered the essence of this type of genetics. Also in my abstract, we examined the types of study of human heredity. Their varieties and the essence of each method.

Literature

·Encyclopedia. Human. volume 18. part one. Volodin V.A. - M .: Avolta +, 2002;

·Biology. General patterns. Zakharov V.B., Mamontov S.G., Sivoglazov V.I. - M .: School-Press, 1996;

·<#"justify">Application

Table No. 1 Dominant and recessive traits in humans (for some traits, the genes that control them are indicated)

DominantnyeRetsessivnyeNormalnaya pigmentation of the skin, eyes, volosAlbinizmBlizorukostNormalnoe zrenieNormalnoe zrenieNochnaya slepotaTsvetovoe zrenieDaltonizmKataraktaOtsutstvie kataraktyKosoglazieOtsutstvie kosoglaziyaTolstye gubyTonkie gubyPolidaktiliya (extra toes) Average number paltsevBrahidaktiliya (short fingers) Normal paltsevVesnushkiOtsutstvie length vesnushekNormalny sluhVrozhdennaya gluhotaKarlikovostNormalny rostNormalnoe assimilation glyukozySaharny diabetNormalnaya clotting kroviGemofiliyaKruglaya face shape (the R-) square face shape (rr) Dimple on the chin (A-) No dimples (aa) Dimples on the cheeks (D-) No dimples (dd) Thick eyebrows (B-) Thin eyebrows (bb) Eyebrows do not join (N-) Eyebrows join (nn) Long eyelashes ( L-) Short eyelashes (ll) Round nose (G-) Pointed nose (gg) Round nostrils (Q-) Narrow nostrils (qq)

Table No. 2 Incomplete dominance (the genes that control the trait are indicated)

SignsVariantsEye Distance - TLargeMediumSmallEye Size - ELargeMediumSmallMouth Size - MBLargeMediumSmallHair Type - CurlyCurlyStraightEyebrow Color - NIGHT DarkDarkLightLargeMedium Nose Size Table No. 3 Inheritance of hair color (controlled by four genes, polymeric inherited)

Number of dominant alleles Hair color8Black7Dark brown6Dark brown5Cubber4Dark blond3Light blond2Blond1Very light blonde0White

Table No. 4

a) The degree of difference (discordance) in a number of neutral traits in twins

Signs controlled by a small number of genes The frequency (probability) of the appearance of differences,% Heritability,% identical, different eggs Eye color 0.57299 Ear shape 2.08098 Hair color 3.07796 Papillary lines 8.06087 average< 1 %≈ 55 %95 %Биохимические признаки0,0от 0 до 100100 %Цвет кожи0,055Форма волос0,021Форма бровей0,049Форма носа0,066Форма губ0,035

b) The degree of similarity (concordance) for a number of diseases in twins

Traits controlled by a large number of genes and dependent on nongenetic factors Frequency of occurrence of similarity,% Heritability,% identical fraternal Mental retardation 973795 Schizophrenia 691066 Diabetes mellitus 651857 Epilepsy 673053 average ≈ 70% ≈ 20% ≈ 65% Crime (?) 682856%

Table No. 5

Types and names of mutations Mutation frequency (per 1 million gametes) Autosomal dominant Polycystic kidney disease 65 ... 120 Neurofibromatosis 65 ... 120 Multiple colon polyposis 10 ... 50 Pelger's leukocyte anomaly 9 ... 27 Osteogenesis imperfecta 7 ... 13 6 Marfan's syndrome 4 ... not sex-linked) 11 Recessive, sex-linked Duchenne muscular dystrophy 43 ... 105 Hemophilia A37 ... 52 Hemophilia B2 ... 3 Ichthyosis (sex-linked) 24

Clinical and genealogical method was introduced at the end of the 19th century by F. Galton. It is based on the construction of pedigrees and tracing the transmission of a certain trait in a series of generations.

Genealogical analysis stages:

1) collection of data on all relatives of the subject (anamnesis);

2) building a pedigree;

3) analysis of the pedigree and conclusions.

The method allows you to set:

1) whether the given trait is hereditary;

2) the type and nature of inheritance;

3) zygosity of persons of pedigree;

4) gene penetrance,

5) the likelihood of having a child with this hereditary pathology.

Compilation of a pedigree start by collecting information about the family of the counselor or proband. Consulting is the name of the person who seeks a doctor, or the first person that comes into the field of view of the researcher. Proband- a patient or a carrier of the studied trait. In many cases, the consultant and the proband are the same person. Children of one parental couple are called siblings(brothers and sisters). Family in a narrow sense, the parent couple and their children are called, but sometimes a wider circle of blood relatives, although in the latter case it is better to use the term genus. The difficulty of collecting anamnesis lies in the fact that the proband should know well, if possible, most of his relatives and their state of health.

Clinical and syndromological method allows you to identify morphological, biochemical and functional signs of hereditary forms of pathology (for example, a deficiency of plasma factor VIII with suspected hemophilia A; karyotype 45, X0 with suspected Shereshevsky-Turner syndrome; lesions of the skeleton, CVS and eyes in case of suspected Marfan syndrome).

Twin method the study of human genetics was introduced into medical practice by F. Galton in 1876. It makes it possible to determine the role of genotype and environment in the manifestation of traits.

Distinguish between mono- and dizygotic twins. Monozygous(identical) Twins develop from one fertilized egg, have exactly the same genotype, and if they differ phenotypically, then this is due to the influence of environmental factors. Dizygotic(double-faced) Twins develop after fertilization by spermatozoa of several simultaneously matured eggs, will have a different genotype, and their phenotypic differences are due to both the genotype and environmental factors. Monozygotic twins have a high degree of similarity in traits, which are determined mainly by the genotype. For example, monozygous twins are always same sex, they have the same blood groups for different systems (ABO, Rh, MN, etc.), the same eye color, dermatoglyphic indicators of the same type on fingers and palms, etc. These phenotypic signs are used as criteria for the diagnosis of zygosity in twins.

The percentage of similarity of a group of twins according to the studied trait is called concordance, and the percentage of difference is discordance... Since monozygous twins have the same genotype, their concordance is higher than that of dizygotic twins.

To assess the role of heredity and the environment in the development of a particular trait, use Holzinger's formula:

KMB% - KDB%

where H is the proportion of heredity, KMB% is the concordance of monozygotic twins, and KDB% is the concordance of dizygotic twins.

Population statistical method the study of human genetics is based on the use Hardy-Weinberg law... It allows you to determine the frequency of genes and genotypes in human populations. For example, homozygotes for the HbS gene are practically not found in Belarus, and in West African countries their frequency varies from 25% in Cameroon to 40% in Tanzania. The study of the distribution of genes among the population of different geographic zones (genogeography) makes it possible to establish the centers of origin of various ethnic groups and their migration, to determine the degree of risk of hereditary diseases in individual individuals.

Cytogenetic method based on microscopic examination of chromosomes in order to identify structural abnormalities in the chromosome set (karyotyping). The material used is tissue cultures with a large number of dividing cells, more often peripheral blood lymphocytes. Chromosomes at the metaphase stage are studied using special staining methods and idiograms are drawn up (systematized karyotypes with the arrangement of chromosomes from largest to smallest).

Method steps:

1) cultivation of human cells (usually lymphocytes) on artificial nutrient media;

2) stimulation of mitosis by phytohemagglutinin (PHA);

3) the addition of colchicine (destroys the spindle filaments) to stop mitosis at the metaphase stage;

4) treatment of cells with a hypotonic solution, as a result of which the chromosomes disintegrate and lie free;

5) staining of chromosomes;

6) examination under a microscope and photography;

7) cutting out individual chromosomes and building an idiogram.

The method allows detecting genomic (for example, Down's disease) and chromosomal (eg, cat cry syndrome) mutations. Chromosomal aberrations are indicated by the number of the chromosome, the short or long arm, and the excess (+) or lack (-) of genetic material. For example, the syndrome of a feline cry is denoted: 5p-.

Biochemical methods are based on the study of the activity of enzyme systems (either by the activity of the enzyme itself, or by the amount of end products of the reaction catalyzed by this enzyme). They allow you to identify gene mutations - the causes of metabolic diseases (for example, phenylketonuria, sickle cell anemia). Biochemical stress tests can be used to identify heterozygous carriers of pathological genes, such as phenylketonuria. The test person is injected intravenously with a certain amount of the amino acid phenylalanine and at regular intervals determine its concentration in the blood. If a person is homozygous for the dominant gene (AA), then the concentration of phenylalanine in the blood quickly returns to the control level (determined before the introduction of phenylalanine), and if he is heterozygous (Aa), then the decrease in the concentration of phenylalanine is twice as slow. Similarly, tests are carried out that reveal a predisposition to diabetes mellitus, hypertension and other diseases.

Research objects:

· Metabolites in biological fluids and cells (for example, phenylalanine in phenylpyruvic oligophrenia; ketone bodies (CT) in diabetes mellitus);

• abnormal proteins (for example, Hb in hemoglobinopathies);

Defective enzymes (eg cholinesterase, glutathione peroxidase, catalase).

Research stages:

· The first - the use of screening diagnostic programs (for example, thin layer chromatography, electrophoresis, microbiological methods);

· The second - the use of confirmatory methods (for example, fluorometric, spectrophotometric, quantitative determination of metabolites, testing of enzyme activity).

Molecular diagnostics. These methods allow you to analyze DNA fragments, find and isolate individual genes and gene segments and establish the sequence of nucleotides in them. For widespread use in practical health care of recombinant DNA methods, it is necessary to create libraries of radioactive probes for all DNA sequences of the human genome, which is now being successfully performed.

1. DNA cloning method allows you to isolate individual genes or their parts, transcribe (create copies of them) and translate isolated genes. This became possible thanks to the discovery of restriction enzymes.

2. Nucleic acid hybridization. In this method, linear sections of double-stranded DNA are heat-treated and single-stranded fragments are obtained (denaturation). Denatured DNA is incubated under such conditions (t = 37 ° C) when hybridization occurs, i.e. mutual recognition of two complementary strands through pairing of nitrogenous bases. Often a single radioactive strand of DNA is used as a "probe" to identify the order of nucleotides. Both fully and partially homologous sequences can be identified. The specificity of nucleic acid hybridization makes it possible to detect a single gene among tens of thousands. Various modifications of this method allow the clinic to analyze very small amounts of DNA taken from a patient.

Blot hybridization. To identify the genes of interest (including mutant) genes, DNA is subjected to restriction. The obtained DNA fragments are subdivided by molecular weight, denatured and transferred to a carrier (nylon or other membrane). The DNA spotted on the carrier is hybridized with a radiolabelled DNA or RNA probe. As a result, the position of the abnormal DNA fragment is determined.

3. Polymerase chain reaction (PCR) is used to study the regions of suspected mutations and other features of the structure of DNA. For research, you can use any biological material containing DNA (for example, a piece of tissue, a drop or stain of blood, rinsing the mouth, hair follicle). At the first stage, the analyzed DNA is subjected to annealing: it is cleaved into two strands when heated to 95-98 ° C. Then one of the strands is hybridized and the synthesis of a sequence complementary to the DNA under study is stimulated (using thermophilic DNA polymerase). In the first cycle of PCR, hybridization is performed with the investigated DNA fragment, and in subsequent ones - with newly synthesized ones. With each cycle of the reaction, the number of synthesized copies of the DNA region doubles. The cycles are repeated until the required amount of DNA has accumulated. This technique was developed and proposed Carey Mullis.

Somatic cell genetics methods make it possible to study many issues of human genetics in experiment. For cultivation, connective tissue cells (fibroblasts) and blood lymphocytes are more often used. On artificial nutrient media, they can be clone, i.e. get descendants of one cell. They will all have the same genotype (like monozygous twins) and, therefore, at the cellular level, the role of genotype and environment in the manifestation of traits can be studied.

Can be carried out selection cells - selection of cells with predetermined properties. For this, selective nutrient media are used. For example, if not lactose, but other sugars are added to the nutrient medium, then from a large number of cells there will be several that can exist without lactose, and in the future it is possible to obtain a clone of such cells.

Of greatest interest for human genetics is the method hybridization somatic cells. In 1960, a French scientist J. Barsky, growing in cell culture two lines of mice, found that some of them in their morphological and biochemical properties were intermediate between the original parental cells. They were hybrid cells. Such spontaneous fusion of somatic cells in tissue culture occurs quite rarely. Later it was found that when the RNA-containing Sendai parainfluenza virus, inactivated by ultraviolet irradiation, is introduced into the cell culture, the frequency of cell hybridization increases significantly, and different types of cells are formed in a mixed culture heterokaryons- cells containing two nuclei of different cells in one cytoplasm. Some of these cells are capable of multiplying by mitosis. After mitosis, two mononuclear cells are formed from a binuclear heterokaryon, each of which is syncarion- a true hybrid cell containing the chromosomes of both original cells.

Hybridization is possible not only between cells of organisms of different species, but also between types: human-mouse, human-mosquito, etc. Syncarions are usually obtained by hybridization of cells of different species belonging to the same class. In such synkarions, the genomes of two types are combined. For example, hybrid cells of a human and a mouse have 43 pairs of chromosomes: 23 from a human and 20 from a mouse. Subsequently, there is a gradual removal of the chromosomes of the organism, the cells of which have a slower rate of reproduction. Human chromosomes are removed from human-mouse hybrid cells. In hybrid cells, the chromosomes of both humans and mice function, the genes of which determine the synthesis of the corresponding proteins. Each of the chromosomes can be distinguished morphologically (differential staining). If in a hybrid cell there is no chromosome and synthesis of some proteins does not occur, then it can be assumed that the genes that determine the synthesis of these proteins are localized in this chromosome. Thus, the method makes it possible to establish linkage groups in humans, and using deficiencies and translocations, to find out the sequence of the location of genes, i.e. build genetic maps of chromosomes person.

Biological modeling certain hereditary human anomalies can be carried out on mutant lines of animals with similar disorders. For example, in dogs, hemophilia occurs due to a recessive X-linked (sex-linked) gene; non-union of lip and palate in mice is similar to similar human anomalies; hamsters and rats have diabetes mellitus, achondroplasia, muscular dystrophy, etc. Although mutant animal lines do not give an accurate picture of hereditary human diseases, even partial reproduction of their fragments in some cases allows studying the mechanisms of primary deviation from the norm. N. I. Vavilov's law of homologous series (species and genera genetically close have similar series of hereditary variability) allows, with certain restrictions, to extrapolate experimental data to a person.

Math modeling is a method of creating and studying mathematical models. It is used to calculate gene frequencies in populations under various influences and environmental changes. Mathematical methods are widely used in cases where it is impossible to use experimental methods (for example, analysis of a large number of linked genes in humans).

Medical genetics studies the role of heredity and variability in the occurrence, development and outcomes of human pathology, develops methods for the diagnosis, treatment and prevention of hereditary and non-hereditary diseases.

Medical genetics as a science is based on a number of fundamental provisions that reveal the essence of the problem of hereditary human diseases and are currently accepted as axioms:

Hereditary diseases are part of the general hereditary variability of a person. There is no sharp borderline between hereditary variability, leading to a change in normal characters, and variability, leading to the emergence of hereditary diseases;

Participate in the development of hereditary traits or diseases hereditary constitution and external environment... At the same time, for the development of some traits or diseases, heredity plays a decisive role, while for others the external environment is essential, but there are no traits that would depend only on heredity or only on the environment;

The hereditary burden of modern humanity is from pathological mutations accumulated in the process of evolution and from newly emerging hereditary changes in germ cells. The quantitative volume of newly emerging mutations may increase under the influence of mutagenic environmental factors:

Ionizing radiation;

Chemical substances;

Other impacts;

human habitat continues to change, which leads to the emergence of new types of hereditary pathology - ecogenetic diseases since changes genetic structure of human populations:

The circle of potential marriage partners has expanded;

Migration of the population has reached a wide scale;

Modern medicine has great potential in the diagnosis, treatment and prevention of hereditary diseases, and in the future it will have even more. A sick person or a carrier of a pathological incline is a full member of society and has equal rights with a healthy person. The progress of medicine and society leads to the following:

Increasing the life expectancy of patients with hereditary diseases;

Restoration of their reproductive function;

And, consequently, the growth of their number in the population.

Medical genetics helps to understand the interaction of biological and environmental factors in human pathology. On the basis of medical and genetic knowledge, the skills of diagnosing hereditary diseases are acquired.

Currently, there is a slender system for the prevention of hereditary diseases, which includes:

Medical genetic counseling;

Perinatal diagnostics;

Mass diagnostics in newborns of hereditary metabolic diseases amenable to dietary and drug therapy;

Clinical examination of patients and their families.

The introduction of this system has reduced the frequency of birth of children with congenital malformations and hereditary diseases by 60-70%.

Based on the achievements of genetics already implemented in practical health care, the following prospects can be predicted:

Wide application preimplantation diagnosis in the main medical genetic centers;

Carrying out genetic testing on diseases with a hereditary predisposition and the adoption, according to the results obtained, of preventive measures;

Creation of new approaches and methods of treatment (including gene therapy certain diseases);

Production new types of drugs based on gene information;

Middle-aged and older populations can be screened for the risk of many diseases that can be prevented or alleviated by dietary or drug exposure;

Individual drug susceptibility testing molecular genetic method should become a standard procedure before any medical treatment.

MEDICAL-GENETIC COUNSELING

The branch of preventive medicine, the main goal of which is to prevent the birth of children with hereditary pathology. The emergence of genetic counseling as an independent institution is usually associated with the name S.S. Reed (1947), however, back in the 30s, a Russian clinician-geneticist S.N. Davidenkov carried out genetic counseling and formulated the main provisions on the methodology of counseling families with hereditary diseases of the nervous system (1934). Modern genetic counseling is designed to serve the interests of the family and society.

Purpose of genetic counseling- Establishing the degree of genetic risk in the examined family and explaining to the spouses in an accessible form of the medico-genetic report.

Tasks of medical genetic counseling:

1) pro- and retrospective (before and after birth) counseling for families and patients with hereditary or congenital pathology;

2) prenatal diagnostics of congenital and hereditary diseases;

3) assistance to doctors of various specialties in making a diagnosis of the disease, if this requires special genetic research methods;

4) an explanation in an accessible form to the patient and his family of the degree of risk of having sick children and help them in making a decision;

5) maintaining a territorial register of families and patients with hereditary and congenital pathology and their dispensary observation;

6) propaganda of medico-genetic knowledge among the population.

In short, the task of genetic counseling is to make a genetic prognosis in the family of an individual with an abnormality in physical, mental or sexual development and the choice of preventive measures to prevent the birth of a sick child.

Making a genetic prognosis.

1. Determination of the degree of genetic risk. Genetic risk is understood as the probability of a certain anomaly in the patient (proband) or his relatives, which is expressed as a percentage (from 0 to 100%). The general risk of a genetically determined anomaly for European populations is 3-5% (genetic load), therefore a risk that does not exceed 5% is regarded as low. The genetic risk up to 10% is called mildly increased, up to 20% - moderately increased and over 20% - high. From a genetic point of view, you can neglect the risk that does not go beyond the increased to a mild degree, and not consider it a contraindication to further childbirth, even when there is no possibility of prenatal diagnosis of the alleged anomaly. Genetic risk medium is regarded as a contraindication to childbirth, i.e. as an indication for termination of pregnancy, if the family does not want to be at risk.

Man is an inconvenient subject for the study of genetics. This is due to the biological and social characteristics of human life. Therefore, special methods are used to study human genetics, which allow predicting risks and preventing fatal diseases.

Goals

The developed research methods of human genetics pursue an important goal - to find a way to prolong life and improve the health of the population. Perhaps, in the future, geneticists will solve the problem of aging, learn to correct the genetic code, which will reduce the predisposition and development of incurable genetic diseases.

Modern human genetics studies various aspects of life associated with genetic material and affects the following problems:

the genetic foundations of the physiological and anatomical features of tissues, organs, the body as a whole;
reasons for predispositions, abilities and talents in a particular field of activity;
patterns of distribution of genes between offspring;
causes and ways of preventing genetic diseases;
genetic conditioning of the work of memory, thinking, emotions;
mechanisms of occurrence of beneficial and harmful mutations.

Human genetics is closely related to medicine and anthropology. With knowledge of genetics, medical scientists find ways to combat pathologies of the nervous, humoral, circulatory systems, and oncological diseases. Reading genetic information helps the study of human evolution.

Methods

Human research faces several biological and socio-ethical challenges.
Biological problems include:

work with a large number of chromosomes;
late human puberty;
a long period of pregnancy - the inability to obtain offspring in a short time;
long generational change (over 20-25 years);
low fertility - one or two offspring per pregnancy.

Rice. 1. Human karyotype.

The social problems of studying human heredity are:

impossibility of experimental crossing - it is impossible to use human life for scientific purposes;
the complexity of creating equal conditions for the observation environment - each person is unique due to social upbringing and character traits, therefore it is almost impossible to level even two lives.

The main methods of study are described in the table of methods for the study of human genetics.

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*Method*	*Description*	*Meaning*
Population-statistical	Collection and analysis of statistical data of a group of people (representatives of the same population)	Prediction of the spread of diseases and inheritance of traits in the population
Biochemical	Detects disorders in the functioning of genes that are responsible for metabolism	Revealing a predisposition to various metabolic diseases - diabetes mellitus, phenylketonuria, lactase deficiency
Dermatoglyphic	Study of the skin relief on the fingers (fingerprinting), palms (palmoscopy), soles of the feet (plantoscopy)	Used for personality identification, in the diagnosis of hereditary diseases, in forensic medicine
Twin	Study and comparison of phenotypes and genotypes of identical and fraternal twins in different conditions	The ability to track the influence of the external environment on the development of a certain symptom or disease (schizophrenia, epilepsy)
Genealogical	Studying a person's pedigree in order to observe the inheritance of phenotypic traits and predispositions to diseases in subsequent generations. Identification of dominant and recessive genes	Polydactyly (six-fingered), diabetes mellitus, early baldness, albinism, deafness, poliomyelitis, etc. are monitored.
Cytogenetic	Analysis of the karyotype in normal conditions and in the presence of pathology	Study of chromosomal diseases - Down syndrome, Klinefelter, Turner-Shereshevsky, cat cry syndrome

Rice. 2. A genealogical method for tracing hemophilia.

Population genetics studies the genetic traits of a population. When predicting the transmission of hereditary information, the features of the gene pool, the frequencies of genes and genotypes, phenotypic characteristics of the population, the system of marriages, etc. are taken into account.

Human genetics has both basic specific methods research: genealogical, twin, cytogenetic, population-statistical, ontogenetic, dermatoglyphics, modeling of hereditary diseases and hybridization of somatic cells; methods of molecular genetics; so and additional, used in conjunction with the main (biochemical, microbiological, immunological, etc.).

Genealogical method based on the analysis of the inheritance of human properties and traits by pedigrees. The method was first proposed by F. Galton, conventions (symbols) - by Yust. It includes two stages:

drawing up a pedigree,
genealogical analysis.

Compilation of a pedigree consists of the collection of information about the family, starting with the proband, and a graphic representation of the pedigree using standard conventions (symbols). Genealogical analysis allows you to set:

determine the type of inheritance (autosomal dominant, autosomal recessive, sex-linked) and genotypes of members of the pedigree;
predict the likelihood of manifestation of a trait in the offspring.

All types of inheritance have specific characteristics, the characteristic features of which are manifested in the genealogy. The analysis is based on the genetic patterns of monogenic inheritance of mendelian traits. Mendelian trait is discrete, it is determined by the presence of its allele and obeys the law of splitting. The discreteness of the trait can be assessed by morphological, physiological, biochemical, clinical, immunological criteria

Twin method is the study of twin pairs by establishing intra-pair similarity (concordance) and differences (discordance) between them. Twins- these are children born and born by the same mother at the same time; most often two twins are born. They can be monozygous or dizygotic. Monozygous(identical, MB) develop from one zygote (polyembryonic phenomenon). They are of the same sex and have the same genotype. Dizygotic twins(bilingual, DB) develop from two zygotes (the phenomenon of polio); have different genotypes; can be of the same or different sex. In genetic studies, it is important to establish the zygosity of twins (mono- or dizygotic). To do this, use polysymptomatic method- a number of criteria and clearly inherited traits (eye color, hair color, blood type, etc.) that are least influenced by the environment. After establishing zygosity, the twins of the same pair are compared according to the studied (qualitative or quantitative) trait.

The twin method is used to study the relative role of heredity and the environment in the development of a trait (calculating the heritability coefficient), establishing the hereditary nature of a trait, identifying the causes of different gene penetrance, evaluating the effectiveness of the influence of external factors on a person (drugs, teaching and upbringing methods).

Cytogenetic method - a method of microscopic study of hereditary cell structures - chromosomes. It includes karyotyping and sex chromatin determination. Karyotyping performed to obtain metaphase chromosomes. Karyotype- This is a diploid set of chromosomes in somatic cells at the metaphase stage, characteristic of this species. The karyotype, presented in the form of a diagram, is called idiogram, karyogram, or chromosome complex... For karyotyping, the most convenient source of cells is lymphocytes (peripheral blood cells). First, a sufficient number of dividing cells are obtained (stimulation of PHA), and then metaphase plates (colchicine is used to stop division at the metaphase stage) with separate chromosomes (hypotonic solution). The preparations are stained and photographed, the chromosomes are cut out and laid out. Each chromosome has its own individual pattern, a clear differentiation in length into light and dark stripes - disks (segments).

Determination of X-sex chromatin... Sex chromatin (Barr's body) is a compact dark lump that is found in the interphase nucleus of somatic cells in normal women. Sex chromatin is a coiled X chromosome. Inactivation of one of the X chromosomes is a mechanism that evens out the balance of genes in the male and female body. According to the hypothesis of Maria Lyon, the inactivation of the X chromosome occurs at the early stages of embryogenesis (day 14), it is random, and only the long arms of the X chromosome are inactivated. By the number of lumps of sex chromatin, one can judge the number of X chromosomes (formula n + 1, where n is the number of Barr's bodies). For any number of X chromosomes, only one X chromosome will be active.
Prenatal diagnostic methods designed to prevent the birth of a child with pathology (primary prevention of hereditary diseases). The choice of method depends on the specific situation in the family and the condition of the pregnant woman. Screeners (indirect) are aimed at examining pregnant women and allow identifying a risk group among them. This group of methods includes: blood test for alpha-fetoprotein (allows you to diagnose some fetal malformations - neural tube defects, anencephaly, congenital skin defects, as well as chromosomal diseases), determination of the level of chorionic gonadotropin (increases with Down's disease), determination of the level of unrelated estriol (decreases with Down's disease).

Direct methods are aimed at examining the fetus and are divided into non-invasive (without surgery) and invasive (with a violation of the integrity of the fetal tissue). Non-invasive ultrasound examination, which allows diagnosing multiple pregnancies, anencephaly, defects of the skeletal system, neural tube, atresia of the gastrointestinal tract, is referred to as non-invasive. Direct invasive methods: chorion biopsy (taking the epithelium of the chorionic villi between 8 and 10 weeks of gestation), placentobiopsy (obtaining pieces of the placenta from 7 to 16 weeks), amniocentesis (procedure for obtaining amniotic fluid with a small number of germ cells, performed at 15-18 weeks pregnancy for certain indications), fetal skin biopsy.

Modeling method for hereditary diseases ... Biological modeling is based on the law of homologous series of hereditary variability of N.I. Vavilov, according to which genetically close genera and species are characterized by similar series of hereditary variability. Phylogenetically related organisms show unambiguous responses to certain environmental influences, including the effects of mutagenic factors. Using mutant animal lines, one can create models of hereditary diseases that can occur in animals and humans (hemophilia, diabetes mellitus, epilepsy, achondroplasia), study the mechanisms of their occurrence, the nature of inheritance, and develop diagnostic methods.

Ontogenetic (biochemical) method ... The method is based on the use of biochemical techniques to identify metabolic disorders in the individual development of the organism caused by a mutant gene (gene - enzyme - trait). The change in the enzyme leads to the appearance of intermediate metabolic products in the body. Their determination in blood, urine is used to diagnose enzymopathies.

Population statistical method ... The method is based on the study of the genetic composition of populations. It allows you to estimate the probability of birth of persons with a certain phenotype in a given population group, to calculate the frequency of various alleles of genes and genotypes for these alleles in the population.

Molecular genetics methods ... In molecular genetics, the method of genetic engineering is used (isolation, cloning of genes, creation of recombinant DNA molecules, their introduction into the cell); method of polymerase chain reactions (PCR) - newly synthesized chains of nucleic acids are a matrix in the following replication cycles; sequencing method and

Modern genetics studies the phenomena of heredity and variability, relying on the achievements of various industries, biology - biochemistry, biophysics, cytology, embryology, microbiology, zoology, botany, plant growing and animal husbandry. Genetic research has significantly enriched the theoretical areas of biology, as well as animal science, veterinary medicine, breeding and breeding of farm animals, plant breeding and seed production, and medicine.

The main objects of genetic research at the molecular level are nucleic acid molecules - DNA and RNA, which ensure the preservation, transmission and implementation of hereditary information. The study of the nucleic acids of viruses, bacteria, fungi, plant and animal cells cultivated outside the body (in vitro) makes it possible to establish the regularities of the action of genes during the life of the cell and the body.

The branch of genetics that studies the phenomena of heredity at the cellular level is called cytogenesis. The cell is an elementary system that contains in full the genetic program of the individual's individual development. The main objects of research using cytological methods are plant and animal cells both inside the body (in vivo) and outside the body, as well as viruses and bacteria. In recent years, research has been carried out on somatic cells that multiply outside the body. Particular attention is paid to the study of chromosomes and some other organelles of the cell containing DNA - mitochondria, plastids, plasmids, as well as ribosomes, on which the synthesis of polypeptide chains - primary protein molecules - is carried out.

The hybridological method was first developed and applied by G. Mendel in 1856-1863. to study the inheritance of traits and has since been the main method of genetic research. It includes a system of crosses of pre-selected parental individuals differing in one, two or three alternative traits, the inheritance of which is "being studied. A thorough analysis of the hybrids of the first, second, third, and sometimes subsequent generations according to the degree and nature of the manifestation of the studied traits is carried out. important in the breeding of plants and animals.It also includes the so-called recombination method, which is based on the phenomenon of crossing-over - the exchange of identical regions in the chromatids of homologous chromosomes in prophase I. This method is widely used to draw up genetic maps, as well as to create recombinant molecules DNA containing the genetic systems of various organisms.

The monosomal method makes it possible to establish in which chromosome the corresponding genes are located, and in combination with the recombination method, to determine the place of localization of genes in the chromosome.

The genealogical method is one of the hybridological options. It is used to study the inheritance of traits by analyzing pedigrees, taking into account their manifestation in animals of related groups in several generations. This method is used in the study of heredity in humans and animals, the infertility of which is specific.

The twin method is used to study the influence of certain environmental factors and their interaction with the genotype of an individual, as well as to identify the relative role of genotypic and modification variability in the overall variability of a trait. Twins are the offspring born in the same litter of singleton domestic animals (cattle, horses, etc.).

There are two types of twins - identical (identical), with the same genotype, and non-identical (different), arising from separately fertilized two or more eggs.

The mutation method (mutagenesis) makes it possible to establish the nature of the influence of mutagenic factors on the genetic apparatus of a cell, DNA, chromosomes, on changes in traits or properties. Mutagenesis is used in the selection of agricultural plants, in microbiology to create new strains of bacteria. It has found application in the breeding of the silkworm.

The population-statistical method is used to study the phenomena of heredity in populations. This method makes it possible to establish the frequency of dominant and recessive alleles that determine a particular trait, the frequency of dominant and recessive homozygotes and heterozygotes, the dynamics of the genetic structure of populations under the influence of mutations, isolation and selection. The method is the theoretical basis for modern animal breeding.

The phenogenetic method makes it possible to establish the degree of influence of genes and environmental conditions on the development of the studied properties and traits in ontogenesis. Changes in the feeding and keeping of animals affect the nature of the manifestation of hereditary traits and properties.

An integral part of each method is statistical analysis - the biometric method. It is a series of mathematical techniques that allow you to determine the degree of reliability of the data obtained, to establish the likelihood of differences between the indicators of the experimental and control groups of animals. An integral part of biometrics is the regression law and the statistical law of heritability established by F. Galton.

In genetics, computer modeling is widely used to study the inheritance of quantitative traits in populations, to assess breeding methods - mass selection, selection of animals by breeding indices. This method is especially widely used in the field of genetic engineering and molecular genetics.