Research methods in genetics table. Methods of human genetics. Methods for studying DNA in genetic research

The use of this method is possible in the case when direct relatives are known - the ancestors of the owner of the hereditary trait ( proband) on the maternal and paternal lines in a number of generations or the descendants of the proband also in several generations. When compiling pedigrees in genetics, a certain system of notation is used. After compiling the pedigree, its analysis is carried out in order to establish the nature of the inheritance of the trait under study.

Conventions adopted in the preparation of pedigrees:
1 - man; 2 - woman; 3 - gender not clear; 4 - the owner of the trait under study; 5 - heterozygous carrier of the studied recessive gene; 6 - marriage; 7 - marriage of a man with two women; 8 - related marriage; 9 - parents, children and the order of their birth; 10 - dizygotic twins; 11 - monozygotic twins.

Thanks to the genealogical method, the types of inheritance of many traits in humans have been determined. Thus, polydactyly (an increased number of fingers), the ability to roll the tongue into a tube, brachydactyly (short fingers due to the absence of two phalanges on the fingers), freckles, early baldness, fused fingers, cleft lip, cleft palate, cataracts of the eyes, are inherited according to the autosomal dominant type. fragility of bones and many others. Albinism, red hair, susceptibility to polio, diabetes mellitus, congenital deafness, and other traits are inherited as autosomal recessive.

The dominant trait is the ability to roll the tongue into a tube (1) and its recessive allele is the absence of this ability (2).
3 - pedigree for polydactyly (autosomal dominant inheritance).

A number of traits are inherited sex-linked: X-linked inheritance - hemophilia, color blindness; Y-linked - hypertrichosis of the edge of the auricle, webbed toes. There are a number of genes located in the homologous regions of the X and Y chromosomes, such as general color blindness.

The use of the genealogical method showed that in a related marriage, compared with an unrelated one, the likelihood of deformities, stillbirths, and early mortality in the offspring increases significantly. In related marriages, recessive genes often go into a homozygous state, as a result, certain anomalies develop. An example of this is the inheritance of hemophilia in the royal houses of Europe.

- hemophilic; - female carrier.

Gemini

This method is used in human genetics to determine the degree of hereditary conditionality of the studied traits. Twins can be identical (they are formed in the early stages of zygote cleavage, when full-fledged organisms develop from two or less often from a larger number of blastomeres). Identical twins are genetically identical. When two or less often more eggs mature and are then fertilized by different spermatozoa, fraternal twins develop. Fraternal twins are no more similar to each other than brothers and sisters born at different times. The frequency of twins in humans is about 1% (1/3 identical, 2/3 fraternal); the vast majority of twins are twins.
Since the hereditary material of identical twins is the same, the differences that arise in them depend on the influence of the environment on gene expression. Comparison of the frequency of similarity for a number of characteristics of pairs of identical and fraternal twins allows us to assess the importance of hereditary and environmental factors in the development of the human phenotype.

Children born at the same time are called twins. They are monozygotic(identical) and dizygotic(variegated).

Monozygotic twins develop from one zygote (1), which is divided into two (or more) parts during the crushing stage. Therefore, such twins are genetically identical and always of the same sex. Monozygotic twins are characterized by a high degree of similarity ( concordance) in many ways.

Dizygotic twins develop from two or more eggs that are simultaneously ovulated and fertilized by different spermatozoa (2). Therefore, they have different genotypes and can be either the same or different sex. Unlike monozygotic twins, dizygotic twins are characterized by discordance - dissimilarity in many ways. Data on the concordance of twins for some signs are given in the table.

signs	Concordance, %
signs	Monozygotic twins	dizygotic twins
Normal
Blood group (AB0)	100	46
eye color	99,5	28
Hair color	97	23
Pathological
Clubfoot	32	3
"Hare Lip"	33	5
Bronchial asthma	19	4,8
Measles	98	94
Tuberculosis	37	15
Epilepsy	67	3
Schizophrenia	70	13

As can be seen from the table, the degree of concordance of monozygotic twins for all the above characteristics is significantly higher than that of dizygotic twins, but it is not absolute. As a rule, the discordance of monozygotic twins occurs as a result of intrauterine development disorders of one of them or under the influence of the external environment, if it was different.

Thanks to the twin method, a person's hereditary predisposition to a number of diseases was clarified: schizophrenia, epilepsy, diabetes mellitus and others.

Observations on monozygotic twins provide material for elucidating the role of heredity and environment in the development of traits. Moreover, the external environment is understood not only as physical factors of the environment, but also as social conditions.

P population-statistical

Population genetics methods are widely used in human research. Intrafamilial analysis of morbidity is inseparable from the study of hereditary pathology, both in individual countries and in relatively isolated population groups. The study of the frequency of genes and genotypes in populations is the subject of population genetic research. This provides information on the degree of heterozygosity and polymorphism of human populations, reveals differences in allele frequencies between different populations.
Believe that Hardy's law? Weinberg suggests that inheritance as such does not change the frequency of alleles in a population. This law is quite suitable for the analysis of large populations where there is free crossing. The sum of the allele frequencies of one gene, according to Hardy's formula? Weinberg p+q=1, in the gene pool of the population is a constant value. The sum of allele genotype frequencies of a given gene p2+2pq+q2=1 is also a constant value. With complete dominance, having established the number of recessive homozygotes in this population (q2 is the number of homozygous individuals for the recessive gene with the aa genotype), it is enough to take the square root of the obtained value, and we will find the frequency of the recessive allele a. The frequency of the dominant allele A will be p = 1 - q. Having thus calculated the frequencies of alleles a and A, it is possible to determine the frequencies of the corresponding genotypes in the population (p2 \u003d AA; 2pq \u003d Aa. For example, according to a number of scientists, the frequency of albinism (inherited as an autosomal recessive trait) is 1 : 20 000 (q2) Consequently, the frequency of allele a in the gene pool will be q2=l/20000 = /l4l and then the frequency of allele A will be

p=1-q. p=1. p=1 – 1/141=140/141.

In this case, the frequency of heterozygous carriers of the albinism gene (2pq) will be 2(140/141) x (1/141) = 1/70, or 1.4%
Statistical analysis of the distribution of individual hereditary traits (genes) in human populations in different countries makes it possible to determine the adaptive value of specific genotypes. Once having arisen, mutations can be passed on to offspring for many generations. This leads to polymorphism (genetic heterogeneity) of human populations. Among the population of the Earth it is almost impossible (with the exception of identical twins) to find genetically identical people. In the heterozygous state, populations contain a significant number of recessive alleles (genetic load), which determine the development of various hereditary diseases. The frequency of their occurrence depends on the concentration of the recessive gene in the population and increases significantly with the conclusion of closely related marriages.

Dermatoglyphic

In 1892 F. Galton, as one of the methods for studying a person, proposed a method for studying the skin comb patterns of fingers and palms, as well as flexion palmar grooves. He established that these patterns are an individual characteristic of a person and do not change throughout life. Currently, the hereditary conditionality of skin patterns has been established, although the nature of inheritance has not been completely elucidated. It is likely that the trait is inherited according to the polygenic type. Dermatoglyphic studies are important in identifying twins. The study of people with chromosomal diseases revealed in them specific changes not only in the patterns of fingers and palms, but also in the nature of the main flexor grooves on the skin of the palms. Less studied are dermatoglyphic changes in gene diseases. Basically, these methods of human genetics are used to establish paternity.

The study of imprints of the skin pattern of the palms and feet. With the existing individual differences in fingerprints, due to the peculiarities of the development of the individual, there are several main classes of them.Peculiar changes in fingerprints and palm patterns have been noted in a number of hereditary-degenerative diseases of the nervous system.Characteristic of Down's disease is a monkey (four-fingered) fold, representing a line passing through the entire palm in the transverse direction.Currently, the method is mainly used in forensic medicine. e.

Biochemical

Hereditary diseases that are caused by gene mutations that change the structure or rate of protein synthesis are usually accompanied by a violation of carbohydrate, protein, lipid and other types of metabolism. Hereditary metabolic defects can be diagnosed by determining the structure of the altered protein or its quantity, identifying defective enzymes, or detecting metabolic intermediates in extracellular body fluids (blood, urine, sweat, etc.). For example, analysis of the amino acid sequences of mutated hemoglobin protein chains made it possible to identify several hereditary defects underlying a number of diseases, ? hemoglobinosis. So, in sickle cell anemia in humans, abnormal hemoglobin due to mutation differs from normal by replacing only one amino acid (glutamic acid with valine).
In healthcare practice, in addition to identifying homozygous carriers of mutant genes, there are methods for detecting heterozygous carriers of certain recessive genes, which is especially important in medical genetic counseling. So, in phenotypically normal heterozygotes for phenylketonuria (a recessive mutant gene; in homozygotes, the metabolism of the amino acid phenylalanine is disturbed, which leads to mental retardation), after taking phenylalanine, its increased content in the blood is detected. In hemophilia, heterozygous carriage of the mutant gene can be established by determining the activity of the enzyme changed as a result of the mutation.

cytogenetic

The cytogenetic method is used to study the normal human karyotype, as well as in the diagnosis of hereditary diseases associated with genomic and chromosomal mutations. In addition, this method is used in the study of the mutagenic action of various chemicals, pesticides, insecticides, drugs, etc.
During cell division at the metaphase stage, chromosomes have a clearer structure and are available for study. The human diploid set consists of 46 chromosomes: 22 pairs of autosomes and one pair of sex chromosomes (XX for women, XY for men). Usually, human peripheral blood leukocytes are examined, which are placed in a special nutrient medium, where they divide. Then preparations are prepared and the number and structure of chromosomes are analyzed. The development of special staining methods has greatly simplified the recognition of all human chromosomes, and in combination with the genealogical method and methods of cell and genetic engineering, it has made it possible to correlate genes with specific regions of chromosomes. The complex application of these methods underlies the mapping of human chromosomes. Cytological control is necessary for the diagnosis of chromosomal diseases associated with ansuploidy and chromosomal mutations. The most common are Down's disease (trisomy on the 21st chromosome), Klinefelter's syndrome (47 XXY), Shershevsky's syndrome? Turner (45 XO), etc. Does the loss of a segment of one of the homologous chromosomes of the 21st pair lead to a blood disease? chronic myeloid leukemia.
Cytological studies of the interphase nuclei of somatic cells can reveal the so-called Barry body, or sex chromatin. It turned out that sex chromatin is normally present in women and absent in men. It is the result of heterochromatization of one of the two X chromosomes in females. Knowing this feature, it is possible to identify gender and identify an abnormal number of X chromosomes.
The detection of many hereditary diseases is possible even before the birth of a child. The method of prenatal diagnosis consists in obtaining amniotic fluid, where the cells of the fetus are located, and in the subsequent biochemical and cytological determination of possible hereditary anomalies. This allows you to make a diagnosis in the early stages of pregnancy and decide whether to continue or terminate it.

Hybridization of somatic cells

With the help of these methods, the heredity and variability of somatic cells are studied, which compensates for the impossibility of applying hybridological analysis to a person. These methods, based on the reproduction of these cells in artificial conditions, analyze the genetic processes in individual cells of the body, and, due to the usefulness of the genetic material, use them to study the genetic patterns of the whole organism.

In human genetic studies, the following techniques are used:

cultivation - allows you to get a sufficient amount of genetic material for various studies;
cloning - obtaining descendants of one cell;
selection of somatic cells using artificial media is used to select cells with properties of interest to the researcher;
hybridization of somatic cells is based on the fusion of co-cultured cells of different types.

Hybrid cells containing 2 complete genomes, during division, usually “lose” chromosomes, preferably of one of the species. Thus, it is possible to obtain cells with the desired set of chromosomes, which makes it possible to study the linkage of genes and their localization in certain chromosomes.

Thanks to the methods of genetics of somatic cells, it is possible to study the mechanisms of the primary action and interaction of genes, the regulation of gene activity. The development of these methods has determined the possibility of accurate diagnosis of hereditary diseases in the prenatal period.

Somatic cell genetics studies the heredity and variability of somatic cells, i.e. body cells, not sex cells. Somatic cells have a whole set of genetic information; they can be used to study the genetic characteristics of an entire organism.

Human somatic cells are obtained for genetic research from the material biopsies(lifetime excision of tissues or organs), when a small piece of tissue is taken for research. As a rule, this is done during operations, when it is necessary to establish whether a given formation, for example, a tumor, has a malignant or benign nature.

Currently, the following methods of somatic cell genetics are used : simple cultivation, hybridization, cloning and selection. simple cultivation- this is the reproduction of cells on nutrient media in order to obtain them in sufficient quantities for cytogenetic, biochemical, immunological and other methods.

At hybridization of somatic cells you can cross cells obtained from different people, as well as human cells with cells from mice, rats, guinea pigs, monkeys and other animals. Such studies make it possible to establish linkage groups, and using chromosomal rearrangements to identify the sequence of genes and build genetic maps of human chromosomes.

Cloning- this is the production of offspring of one cell (clone). All cells as a result of cloning will be of the same genotype.

Selection is the selection of cells with predetermined properties. Then these cells are grown and propagated on special nutrient media. For example, one can use a culture medium without lactose, but with the addition of other sugars, and out of a large number of cells placed in it, there may be a few that can live in the absence of lactose. Then a clone is obtained from such cells.

Modeling method

He studies human diseases on animals that can suffer from these diseases. It is based on Vavilov's law of homologous series of hereditary variability, for example, sex-linked hemophilia can be studied in dogs, epilepsy in rabbits, diabetes mellitus, muscular dystrophy in rats, cleft lip and palate in mice

Models in biology are used to model biological structures, functions and processes at different levels of organization of the living: molecular, subcellular, cellular, organ-systemic, organismic and population-biocenotic. It is also possible to model various biological phenomena, as well as the living conditions of individuals, populations and ecosystems.

In biology, three types of models are mainly used: biological, physico-chemical, and mathematical (logical-mathematical). Biological models reproduce certain conditions or diseases that occur in humans or animals in laboratory animals. This makes it possible to study in the experiment the mechanisms of the occurrence of a given condition or disease, its course and outcome, and to influence its course. Examples of such models are artificially induced genetic disorders, infectious processes, intoxication, reproduction of hypertonic and hypoxic states, malignant neoplasms, hyperfunction or hypofunction of certain organs, as well as neuroses and emotional states. To create a biological model, various methods of influencing the genetic apparatus, infection with microbes, the introduction of toxins, the removal of individual organs or the introduction of their metabolic products (for example, hormones), various effects on the central and peripheral nervous system, the exclusion of certain substances from food, the placement into an artificially created habitat and many other ways. Biological models are widely used in genetics, physiology, and pharmacology.

The modeling method in biology is a tool that allows you to establish ever deeper and more complex relationships between biological theory and experience. In the last century, the experimental method in biology began to run into certain limits, and it became clear that a number of studies are impossible without modeling. If we dwell on some examples of restrictions on the scope of the experiment, then they will be mainly as follows: (19 p15)

Experiments can be carried out only on currently existing objects (the impossibility of extending the experiment to the area of the past);

Intervention in biological systems is sometimes of such a nature that it is impossible to establish the causes of the changes that have appeared (due to interference or for other reasons);

Some theoretically possible experiments are not feasible due to the low level of development of experimental technology;

A large group of experiments related to human experimentation should be rejected on moral and ethical grounds.

But modeling is gaining popularity in the field of biology not only because it can replace experiment. It has a great independent significance, which is expressed, according to a number of authors (19, 20,21), in a number of advantages:

1. Using the modeling method on one set of data, you can develop a number of different models, interpret the phenomenon under study in different ways, and choose the most fruitful of them for theoretical interpretation;

2. In the process of building a model, you can make various additions to the hypothesis under study and obtain its simplification;

3. In the case of complex mathematical models, computers can be used;

4. the possibility of conducting model experiments (synthesis of amino acids according to Miller) opens up (19 p152).

All this clearly shows that modeling performs independent functions in biology and is becoming an increasingly necessary step in the process of creating a theory. However, modeling retains its heuristic value only when the limits of application of any model are taken into account.

Immunogenetic

The immunogenetic method includes serological methods, immunoelectrophoresis, etc., which are used to study blood groups, proteins and enzymes in the blood serum of tissues. It can be used to establish immunological incompatibility, identify immunodeficiency, twin mosaicism, etc.
An important branch of medical genetics is immunogenetics, in particular, the genetics of blood groups. Many major blood group systems are now known. Of these, the AB0 and Rhesus systems are the most studied. For example, consider the Rhesus blood system. In the human genotype there is a dominant gene that determines the formation in the body of a special protein calledRh factor. A person who is homozygous (Rh+ Rh+) or heterozygous (Rh+ rh–) for this trait is Rh-positive, i.e. has this protein in the blood. And in the case of homozygosity for the recessive allele (rh– rh–), there is no Rh factor in the blood. And if it enters the blood of such a person (during a blood transfusion or pregnancy), a protective reaction develops in his body - like any foreign protein, and specific antibodies are formed. Statistics show that among Europeans, approximately 85% of people are Rh-positive and only 15% are Rh-negative.

In marriages of Rh-negative women (genotype rh– rh–) with Rh-positive homozygous men (genotype Rh+ Rh+) due to the dominance of Rh-positive fetus (genotype Rh+ rh–) is Rh-positive and secretes the Rh factor against which in the body mothers produce antibodies, which in turn destroy the hematopoietic system of the fetus. As a result, both the mother and the fetus suffer during pregnancy.

A similar situation may arise in the marriage of an Rh-negative woman with a Rh-positive man who is heterozygous for this trait (Rh+ rh– genotype). However, in this case, the probability of a Rh conflict is halved, because. the fetus may be Rh-negative (genotype rh– rh–), and then there is no conflict with the mother's body.

In addition to the likelihood of the situation of the Rhesus conflict itself, determined solely by the genotypes of the parents, the severity of the developing reaction is also important. In some cases, the Rhesus conflict proceeds almost imperceptibly, in others it can cause the death of the child. Usually more severe consequences are observed in the second and subsequent pregnancies.

Currently, for the treatment of neonatal jaundice caused by Rhesus conflict, after birth, the child is given a complete blood transfusion.

The main methods of studying human genetics:

Genealogical;

twin;

Cytogenetic method;

Population-statistical method;

The genealogical method is based on the compilation of a person's pedigree and the study of the nature of the inheritance of a trait. This is the oldest method. Its essence is to establish pedigree relationships and determine dominant and recessive traits and the nature of their inheritance. This method is especially effective in the study of gene mutations.

The method includes two stages: collection of information about the family for as many generations as possible and genealogical analysis. Pedigree is compiled, as a rule, according to one or more characteristics. For this, information is collected about the inheritance of a trait among close and distant relatives.

Representatives of one generation are placed in one row in the order of their birth.

Then the second stage begins - the analysis of the pedigree in order to establish the nature of the inheritance of the trait. First of all, it is established how the trait manifests itself in representatives of different sexes, i.e. linkage of a trait with sex. Next, it is determined whether the trait is dominant or recessive, whether it is linked to other traits, etc. With the recessive nature of inheritance, the trait appears in a small number of individuals not in all generations. It may be missing from the parents. With dominant inheritance, the trait is often found in almost all generations.

A characteristic feature of the inheritance of sex-linked traits is their frequent manifestation in individuals of the same sex. If this sign is dominant, then it is more common in women. If the trait is recessive, then in this case it is more often manifested in men.

The analysis of numerous pedigrees and the nature of the distribution of the trait in a vast human population helped geneticists establish the nature of the inheritance of many normal human traits, such as curly hair and hair color, eye color, freckle, earlobe structure, etc., as well as such anomalies as color blindness, sickle cell anemia, etc.

Thus, using the pedigree method, the dependence of a trait on genetic material, the type of inheritance (dominant, recessive, autosomal, linked to sex chromosomes), the presence of gene linkage, zygosity (homozygosity or heterozygosity) of family members, the probability of gene inheritance in generations, type of inheritance sign. With autosomal dominant inheritance (the appearance of a trait is associated with a dominant gene), the trait, as a rule, manifests itself in each generation (horizontal inheritance). With autosomal recessive inheritance, the trait rarely appears, not in every generation (vertical inheritance), however, in related marriages, sick children are born more often. In sex-linked inheritance, the frequency of manifestation of a trait in individuals of different sexes is not the same.

The cytogenetic method consists in microscopic examination of the structure of chromosomes and their number in healthy and sick people. Of the three types of mutations, only chromosomal and genomic mutations can be detected under a microscope. The simplest method is express diagnostics - the study of the number of sex chromosomes by X-chromatin. Normally, in women, one X chromosome in the cells is in the form of a chromatin body, while in men, such a body is absent. With trisomy in a sexual pair, women have two bodies, and men have one. To identify trisomy in other pairs, the karyotype of somatic cells is examined and an idiogram is compiled, which is compared with the standard one.

Chromosomal mutations are associated with a change in the number or structure of chromosomes. Of these, under a microscope with special staining, translocations, deletions, and inversions are well detected. During translocation or deletion, chromosomes increase or decrease in size, respectively. And with inversion, the pattern of the chromosome changes (alternation of bands).

Chromosomal mutations can be markers in the cytogenetic method for studying a particular disease. In addition, this method is used to determine the radiation doses absorbed by people and in other scientific studies.

The population-statistical method makes it possible to calculate the frequency of occurrence of normal and pathological genes in a population, to determine the ratio of heterozygotes - carriers of abnormal genes. Using this method, the genetic structure of the population is determined (frequencies of genes and genotypes in human populations); phenotype frequencies; the environmental factors that change the genetic structure of the population are studied. The method is based on the Hardy–Weinberg law, according to which the frequencies of genes and genotypes in numerous populations living in unchanged conditions and in the presence of panmixia (free crossings) remain constant over a number of generations. Calculations are made according to the formulas: p + q = 1, p2 + 2pq + q2 = 1. In this case, p is the frequency of the dominant gene (allele) in the population, q is the frequency of the recessive gene (allele) in the population, p2 is the frequency of dominant homozygotes, q2 – recessive homozygotes, 2pq – frequency of heterozygous organisms. Using this method, it is also possible to determine the frequency of carriers of pathological genes.

cytogenetic method. Human karyotype. Characterization of methods for differential staining of chromosomes. Denver and Paris nomenclature. Classification of chromosomes according to the ratio of the length of the arms and the calculation of the centromere index.

cytogenetic method. The cytogenetic method consists in examining the patient's chromosome set of cells under a microscope. As you know, chromosomes are in a spiralized state in a cell and cannot be seen. In order to visualize the chromosomes, the cell is stimulated and introduced into mitosis. In the prophase of mitosis, as well as in the prophase and metaphase of meiosis, the chromosomes are despiralized and visualized.

During visualization, the number of chromosomes is estimated, an ideogram is made in which all chromosomes are written in a certain order according to the Denver classification. Based on the idiogram, we can talk about the presence of a chromosomal aberration or a change in the number of chromosomes, and, accordingly, the presence of a genetic disease.

Everything methods of differential staining of chromosomes make it possible to reveal their structural organization, which is expressed in the appearance of transverse striation, which is different in different chromosomes, as well as some other details.

Differential staining of chromosomes. A number of staining (banding) methods have been developed that make it possible to identify a complex of transverse marks (bands, bands) on a chromosome. Each chromosome is characterized by a specific set of bands. Homologous chromosomes stain identically, with the exception of polymorphic regions where different allelic variants of genes are localized. Allelic polymorphism is characteristic of many genes and is found in most populations. Detection of polymorphisms at the cytogenetic level has no diagnostic value.

A. Q-staining. The first method of differential staining of chromosomes was developed by the Swedish cytologist Kaspersson, who used for this purpose the fluorescent dye acrichin mustard. Under a fluorescent microscope, areas with unequal fluorescence intensity are visible on the chromosomes - Q-segments. The method is best suited for the study of Y chromosomes and is therefore used to quickly determine the genetic sex, identify translocations(site exchanges) between X- and Y-chromosomes or between Y-chromosome and autosomes, as well as for viewing a large number of cells, when it is necessary to find out whether a patient with mosaicism on sex chromosomes has a clone of cells carrying a Y-chromosome.

B. G-staining. After extensive pretreatment, often with trypsin, the chromosomes are stained with Giemsa stain. Under a light microscope, light and dark stripes are visible on the chromosomes - G-segments. Although the arrangement of the Q segments corresponds to that of the G segments, G staining has proven to be more sensitive and has taken the place of Q staining as the standard method of cytogenetic analysis. G-staining gives the best results in detecting small aberrations and marker chromosomes (segmented differently than normal homologous chromosomes).

B. R-staining gives a picture opposite to G-staining. Usually Giemsa stain or acridine orange fluorescent stain is used. This method reveals differences in staining of homologous G- or Q-negative regions of sister chromatids or homologous chromosomes.

D. C-staining used to analyze the centromeric regions of chromosomes (these regions contain constitutive heterochromatin) and the variable, brightly fluorescent distal part of the Y chromosome.

D. T-staining used to analyze telomeric regions of chromosomes. This technique, as well as staining of regions of nucleolar organizers with silver nitrate (AgNOR-staining) is used to refine the results obtained by standard staining of chromosomes.

The classification and nomenclature of uniformly colored human chromosomes were first adopted at an international meeting in 1960 in Denver, later somewhat modified and supplemented (London, 1963 and Chicago, 1966). According to the Denver classification, all human chromosomes are divided into 7 groups, arranged in decreasing order of their length and taking into account the centriole index (the ratio of the length of the short arm to the length of the entire chromosome, expressed as a percentage). Groups are designated by letters of the English alphabet from A to G. All pairs of chromosomes are usually numbered with Arabic numerals

In the early 70s of the XX century, a method of differential coloration of chromosomes was developed, revealing characteristic segmentation, which made it possible to individualize each chromosome (Fig. 58). Different types of segments are designated by the methods by which they are most clearly identified (Q-segments, G-segments, T-segments, S-segments). Each human chromosome contains a sequence of bands peculiar only to it, which makes it possible to identify each chromosome. Chromosomes are maximally coiled in metaphase, less coiled in prophase and prometaphase, which makes it possible to isolate a larger number of segments than in metaphase.

On the metaphase chromosome (Fig. 59), symbols are given that are used to denote the short and long arms, as well as the location of regions and segments. Currently, there are DNA markers or probes that can be used to determine the change in a certain, even very small, segment in chromosomes (cytogenetic maps). At the International Congress of Human Genetics in Paris in 1971 (Paris Conference on Standardization and Nomenclature of Human Chromosomes), a symbol system was agreed upon for a more concise and unambiguous designation of karyotypes.
When describing a karyotype:
the total number of chromosomes and the set of sex chromosomes are indicated, a comma is placed between them (46, XX; 46, XY);
it is noted which chromosome is superfluous or which is missing (this is indicated by its number 5, 6, etc., or the letters of this group A, B, etc.); the “+” sign indicates an increase in the number of chromosomes, the “-” sign indicates the absence of this chromosome 47, XY, + 21;
arm of the chromosome in which the change occurred (lengthening of the short arm is indicated by the symbol (p+); shortening (p-); lengthening of the long arm is indicated by the symbol (q+); shortening (q-);
rearrangement symbols (translocation is denoted by t, and deletion by del) are placed in front of the numbers of the involved chromosomes, and rearrangement chromosomes are enclosed in brackets. The presence of two structurally abnormal chromosomes is indicated by a semicolon (;) or a normal fraction (15/21).

The role of the twin method in the study of heredity and environment in the formation of traits. Twin types. The problem of predisposition to diseases. Risk factors. Genealogical method (analysis of the family tree). Criteria for determining the type of inheritance.

The twin method is based on the study of the phenotype and genotype of twins to determine the degree of influence of the environment on the development of various traits. Among twins, identical and dizygotic are distinguished.

Identical twins (identical) are formed from one zygote, divided into two parts at an early stage of crushing. In this case, one fertilized egg gives rise to not one, but two embryos at once. They have the same genetic material, are always the same sex, and are the most interesting to study. The resemblance of such twins is almost absolute. Minor differences can be explained by the influence of developmental conditions.

Fraternal twins (non-identical) are formed from different zygotes, as a result of the fertilization of two eggs by two sperm. They resemble each other no more than siblings born at different times. Such twins can be same-sex or opposite-sex.

The twin method allows you to determine the degree of manifestation of a trait in a couple, the influence of heredity and environment on the development of traits. All differences that appear in identical twins with the same genotype are associated with the influence of external conditions. Of great interest are cases when such a couple was separated for some reason in childhood and the twins grew up and were brought up in different conditions.

The study of fraternal twins allows us to analyze the development of different genotypes in the same environmental conditions. The twin method made it possible to establish that for many diseases the environmental conditions under which the phenotype is formed play a significant role.

For example, such traits as blood type, eye and hair color are determined only by the genotype and do not depend on the environment. Some diseases, although caused by viruses and bacteria, depend to some extent on hereditary predisposition. Diseases such as hypertension and rheumatism are largely determined by external factors and to a lesser extent by heredity.

Thus, the twin method makes it possible to identify the role of the genotype and environmental factors in the formation of a trait, for which the degrees of similarity (concordance) and differences (discordance) of monozygotic and dizygotic twins are studied and compared.

The genealogical method consists in the analysis of pedigrees and allows you to determine the type of inheritance (dominant
recessive, autosomal or sex-linked) trait, as well as its monogenicity or polygenicity. Based on the information obtained, the probability of the manifestation of the studied trait in the offspring is predicted, which is of great importance for the prevention of hereditary diseases.

Genealogical analysis is the most common, simplest and at the same time highly informative method available to anyone who is interested in their genealogy and the history of their family

Human genetics studies the phenomena of heredity and variability in human populations, the features of the inheritance of traits in the norm and their changes under the influence of environmental conditions.

Man as an object of genetic analysis. The study of human genetics is associated with great difficulties:

Impossibility of experimentation.

One of the first conditions of hybridological analysis in humans is unfeasible, since experimental marriages in humans are impossible. People get married without any "experimental" goals.

Complex karyotype - many chromosomes and linkage groups.

23 pairs of chromosomes complicates genetic and cytological mapping, which in turn reduces the possibilities of genetic analysis.

duration of generational change.

It takes an average of 30 years to change one generation. Therefore, the geneticist cannot observe more than one or two generations.

Small number of offspring.

The size of the family is currently so small that it does not allow one to analyze the splitting of traits in the offspring within the same family.

The impossibility of creating the same living conditions.

For humans, the concept of "environment" has a broader character than for animals and plants. Aside from factors such as exercise, nutrition, housing, climate, a person's environment is the conditions of his social life, and it is not amenable to change at the request of the geneticist.

Basic methods for studying human genetics

I.Clinical and genealogical method

Genealogy in the broad sense of the word pedigree - genealogical method - method of pedigrees. It was introduced at the end of the 19th century by F. Galton and is based on building pedigrees and tracing a disease (or trait) in a family or genus, indicating the type of family ties between members of the pedigree. At present, it is the most universal and widely used in solving theoretical and applied problems.

The method allows you to set

1) whether this trait is hereditary

2) type of inheritance and gene penetrance

3) suggest the genotype of individuals of the pedigree

4) determine the probability of having a child with the disease under study

5) intensity of the mutation process

6) used to compile genetic maps of chromosomes

Thus, the purpose of the genealogical method is reduced to the clarification of family ties and to tracing a trait or disease among close and distant, direct and indirect relatives. Technically, it consists of the following steps.

Stages of genealogical analysis:

1) collection of data on all relatives of the subject (history)

2) building a pedigree

3) analysis of the pedigree and conclusions

The complexity of taking an anamnesis lies in the fact that the proband should know well the majority of his relatives and their state of health. Proband - a person who applied to a medical genetic consultation, in respect of whom a pedigree is being built, and from whom information was received regarding the same disease from relatives. Sibs are brothers and sisters of the proband.

Inheritance types:

1. Autosomal dominant

1. sick in every generation

2. sick child in sick parents

3. men and women are equally affected

4. inheritance goes vertically and horizontally

5. probability of inheritance 100%, 75% and 50%.

These signs will appear only with complete dominance, as polydactyly, freckles, curly hair, brown eyes, etc. are inherited in humans. With incomplete dominance, an intermediate form of inheritance will appear. With incomplete penetrance of the gene, patients may not be in every generation.

2. Autosomal recessive

sick not in every generation
men and women are affected equally
inheritance is predominantly horizontal
probability of inheritance 25, 50 and 100%

Most often, the probability of inheriting this type of disease is 25%, because due to the severity of the disease, patients either do not live to childbearing age or do not marry. This is how phenylketonuria, sickle cell anemia, blue eyes, etc. are inherited.

3. X-linked recessive type of inheritance

sick not in every generation
healthy parents have a sick child
predominantly men are affected
inheritance is mostly horizontal
probability of inheritance 25% in all children and 50% in boys

Examples: hemophilia, color blindness, hereditary anemia, muscular dystrophy, etc.

4. X-linked dominant the pattern of inheritance is similar to autosomal dominant, except that the male passes this trait to all daughters

Example: rickets resistant to vitamin D treatment, tooth enamel hypoplasia, follicular hyperkeratosis.

5. Hollandic

patients in all generations
only men get sick
a sick father has sick all his sons
the probability of inheritance is 100% in boys.

Examples: hypertrichosis of the auricle, membranes between the second and third toes; a gene that determines the development of the testicles. Hollandic signs are not significant in human hereditary pathology.

II. Cytogenetic method

Currently, the cytogenetic method in genetics occupies a significant place. The use of this method makes it possible to study the morphological structure of individual chromosomes and the karyotype as a whole, determine the genetic sex of the organism, and also diagnose various chromosomal diseases associated with a violation of the number of chromosomes or a violation of their structure. The method is used to study the mutation process and make genetic maps of chromosomes. The method is most often used in prenatal diagnosis of chromosomal diseases.

The cytogenetic method is based on a microscopic study of the karyotype and includes the following steps:

Cultivation of human cells (usually lymphocytes) on artificial nutrient media

Stimulation of mitoses by phytohemagglutinin (PHA)

Addition of colchicine (destroys the spindle fibers) to stop mitosis at the metaphase stage

Treatment of cells with a hypotonic solution, as a result of which the chromosomes crumble and lie freely

Chromosome staining

Microscopic examination (computer programs).

Cytological maps of chromosomes -

Genetic maps of chromosomes, i.e. schemes describing the arrangement of genes and other genetic elements in the chromosome, indicating the distance between them. The genetic distance is determined by the frequency of recombination between homologous chromosomes (the distance between genes is directly proportional to the frequency of crossing over) and is expressed in centimorganides (cM). One centimorganide corresponds to a recombination frequency equal to 1%.............. Such genetic maps, in addition to the inventory of genes, answer the question of the involvement of genes in the formation of individual features of an organism.

The method allows to detect genomic (for example, Down's disease) and chromosomal (cat's cry syndrome) mutations. Chromosomal aberrations are denoted by the number of the chromosome, short or long arm, and excess (+) or lack (-) of genetic material.

III.twin method

The method consists in studying the patterns of inheritance of traits in pairs of monozygotic and dizygotic twins. It allows you to determine the correlative role of heredity (genotype) and environment in the manifestation of various signs, both normal and pathological. Allows you to identify the hereditary nature of the trait, determine the penetrance of the allele, evaluate the effectiveness of the action on the body of some external factors (drugs, training, education).

The essence of the method is to compare the manifestation of a trait in different groups of twins, taking into account the similarity or difference in their genotypes.

There are mono and dizygotic twins.

Monozygotic twins develop from one fertilized egg. They have exactly the same genotype, because. have 100% common genes. And if they differ in phenotype, then this is due to the influence of environmental factors.

Dizygotic twins develop after the fertilization by spermatozoa of several simultaneously matured eggs. Twins will have a different genotype and their phenotypic differences will be due to both genotype and environmental factors.

The percentage of similarity of a group of twins according to the trait under study is called concordance, and the percentage of difference is called discordance. Since monozygotic twins have the same genotype, the trait develops in both twins, their concordance is higher than that of dizygotic twins. Comparison of monozygotic twins brought up in different conditions makes it possible to identify signs in the formation of which environmental factors play a significant role; according to these signs, discordance is observed between the twins, i.e. differences.

To assess whether heredity and environment in the development of a particular trait, the Holzinger formula is used:

S MZ - S DZ

H \u003d --------------------- x 100 E \u003d 100 - H

H - the role of heredity, E - the role of the environment

As the theoretical foundations of the twin method were developed, a special section of these studies was gradually formed - the partner control method. Allows you to evaluate the therapeutic effect of new pharmacological agents with different methods of administration, explore the phases of their action, show the differences in the pharmacokinetics of new and old drugs). The method is used for predisposition to various diseases: ischemic heart disease, peptic ulcer, rheumatism, infectious diseases, tumors.

IV. Population-statistical method

With its help, hereditary traits are studied in large population groups, in one or several generations. It allows you to determine the frequency of occurrence in a population of various alleles of a gene and different genotypes for these alleles, to find out the distribution of various hereditary traits in it, including diseases. It allows you to study the mutation process, the role of heredity and environment in the occurrence of diseases, especially those with a hereditary predisposition. The essential point of using this method is the statistical processing of the data obtained on the basis of the Hardy-Weinberg genetic equilibrium law.

The mathematical expression of the law is the formula (pA + qa) 2 where p and q are the frequencies of occurrence of alleles A and a of the corresponding gene. The disclosure of this formula makes it possible to calculate the frequency of occurrence of people with different genotypes and, first of all, heterozygotes - carriers of the hidden recessive allele: p 2 AA + 2pq + q 2 aa.

However, before talking about the practical application of these formulas, the conditions for the emergence of genotype equilibrium in populations should be noted:

1) The presence of panmixia, i.e. random selection of married couples

2) No influx of alleles caused by mutational pressure

3) The absence of an outflow of alleles caused by selection.

4) Equal fecundity of heterozygotes and homozygotes

5) Generations should not overlap in time

6) The population size must be large enough.

Well-known geneticists note that although this set of conditions cannot be met in any particular population, in most cases the calculations according to the Hardy-Weinberg law are so close to reality that this law is quite suitable for analyzing the genetic structure of populations.

Example……..

For example, there are practically no homozygotes for the HbS gene in Belarus, and in West Africa their frequency varies from 25% in Cameroon to 40% in Tanzania. The study of the distribution of genes among the population of different geographical areas (genogeography) makes it possible to establish the centers of origin of various ethnic groups and their migration, to determine the risk of hereditary diseases in certain individuals.

V. Method of dermatoglyphics and palmoscopy (dactyloscopy)

In 1892, Galton was proposed as one of the methods for studying human genetics - This is a method for studying the skin comb patterns of fingers and palms, as well as flexion palmar grooves. These patterns are an individual characteristic of a person and do not change during his life, they are restored after damage (burns).

Example (Galton, Gioconda)

It has now been established that the trait is inherited according to the polygenic type and the mother has a great influence on the nature of the finger and palmar patterns through the mechanism of cytoplasmic heredity.

The method has found wide application in criminalistics, identification of zygosity of twins, establishment of paternity. Characteristic changes in these patterns are observed in some chromosomal diseases (Sm Down, Klinefelter, Sher.-Turner).

VI. Biochemical methods

Allows you to study hereditary diseases caused by gene mutations - the causes of metabolic diseases (phenylketonuria, sickle cell anemia). Using this method, more than 1000 congenital metabolic diseases have been described, for many of them a defect in the primary gene product has been identified. The most common among these diseases are diseases associated with defective enzymes, structural, transport or other proteins.

The method is based on studying 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.

Enzyme defects are determined by determining the content in the blood and urine of metabolic products resulting from the functioning of this protein. Deficiency of the final product, accompanied by the accumulation of intermediate and by-products of impaired metabolism, indicates a defect in the enzyme or its deficiency in the body.

With the help of biochemical stress tests, heterozygous carriers of pathological genes, such as phenylketonuria, can be detected. The examined person is injected intravenously with a certain amount of the amino acid phenylalanine and its concentration in the blood is determined at regular intervals. If a person is homozygous for the dominant gene (AA), then the concentration of phenylalanine in the blood quickly returns to the control level, 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.

VII. Recombinant DNA methods

They allow analyzing DNA fragments, finding and isolating individual genes and gene segments and establishing the nucleotide sequence in them. This method includes the DNA cloning method. The term “cloning” means that a gene has been cloned, isolated by special techniques, its structure has been studied, gene cloning also means that a protein is known, the synthesis of which is controlled by the corresponding gene. On the basis of cloned genes, "genomic libraries" and international databanks are being created. Any specialist in the world can practically freely enter these databanks and use the information collected there for research purposes. The data of genomic libraries are widely used in the implementation of the "human genome" program. (Collection of DNA fragments from the whole genome)

The success of this program has made it possible to realistically assess the functions of genes in the human body. Although information is not yet available for more than a quarter of the genes, for two-thirds of the genes it is either fully established or can be approximated. Also, exceptionally interesting information was obtained on the involvement of genes in the formation and functioning of individual organs and tissues of the human body. It turned out that the largest number of genes is necessary for the formation of the brain and maintaining its activity, and the smallest for the creation of red blood cells - only 8 genes. This information will help to understand the genetic programs for the development and functioning of the human body, the causes of cancer and aging. Revealing the molecular basis of diseases will help to bring the methods of their early diagnosis to a new level, and, therefore, to conduct a more sophisticated and successful fight against diseases. Methods such as, for example, targeted delivery of drugs to affected cells, replacement of diseased genes with healthy ones, and many others are becoming part of the arsenal of modern medicine.

VIII. Methods of genetics of somatic cells

With the help of these methods, the heredity and variability of somatic cells are studied, which largely compensates for the impossibility of applying the hybridological method to a person.

Human somatic cell cultures are obtained from biopsy material (peripheral blood, skin, tumor tissue, embryonic tissue, cells from amniotic fluid).

In human genetics, the following four methods are used.

1. Simple cultivation - cells are suitable for cytogenetic, biochemical, immunological and other studies.

2. Cloning - obtaining descendants of one cell. It makes it possible to carry out biochemical analysis of genetically determined processes in genetically identical cells.

3. Selection of somatic cells using artificial media is used to select mutant cells with certain properties, the selection of hybrid cells. The method is widely used to study gene mutations (mechanisms, spontaneous and induced frequency).

4. Hybridization of somatic cells is based on the fusion of co-cultured cells of different types. When introduced into cell culture RNA-soda. Sendai virus inactivated by ultraviolet irradiation - the frequency of hybridization is significantly increased. Heterokaryons - 2 nuclei of different cells in the same cytoplasm. After mitosis, two single-nuclear cells are formed - synkaryons - a real hybrid cell containing the chromosomes of both original cells. In the future, there is a gradual removal of the chromosomes of the organism whose cells have a slower rate of reproduction.

The loss of chromosomes is random and therefore among a large number of hybrids one can always find a cell that has retained any one human chromosome.

Using a suitable selection system, cells with a particular enzymatic activity can be selected and the gene for that enzyme can be located on a particular chromosome.

The method is used to study the problem of linkage and localization of genes.

It is possible to study the mechanisms of the primary action and interaction of genes, the regulation of gene activity. The method makes it possible to widely study the pathogenesis of hereditary diseases at the biochemical and cellular level.

IX. Creation of models of human hereditary diseases using transgenic

animals.

Biological modeling of hereditary diseases is a large branch of experimental biology and genetics. The principle of biological modeling of gene mutations is based on the law of homologous series in hereditary variability, discovered by N.I. Vavilov. In animals, there are mutations that cause the same pathological effect as in humans (mice, rabbits, dogs, hamsters, mice). Among hereditary anomalies in animals, there are diseases such as hemophilia, achondroplasia, muscular dystrophy, diabetes mellitus and many others, which form the basis of human hereditary pathology.

The methods are based on the introduction of foreign genes into embryonic cells.

Like any model, mutant lines of transgenic animals cannot fully reproduce a hereditary disease; therefore, some specific fragments are modeled in order to study the primary mechanism of gene action, the pathogenesis of the disease, and develop principles for its treatment.

genealogical method consists in the study of pedigrees based on the Mendelian laws of inheritance and helps to establish the nature of the inheritance of a trait (dominant or recessive).
This is how the inheritance of individual characteristics of a person is established: facial features, height, blood type, mental and mental make-up, as well as some diseases. For example, when studying the genealogy of the royal Habsburg dynasty, a protruding lower lip and a hooked nose can be traced in several generations.
This method revealed the harmful effects of closely related marriages, which are especially evident when homozygous for the same unfavorable recessive allele. In related marriages, the probability of having children with hereditary diseases and early infant mortality is tens and even hundreds of times higher than the average.

twin method is to study the differences between identical twins. This method is provided by nature itself. It helps to identify the influence of environmental conditions on the phenotype with the same genotypes.
Growing up in the same conditions, identical twins have a striking similarity not only in morphological features, but also in mental and intellectual characteristics.
Using the twin method, the role of heredity in a number of diseases was revealed.

population method. Population genetics studies the genetic differences between individual groups of people (populations), explores the patterns of geographical distribution of genes.

Cytogenetic method is based on the study of variability and heredity at the level of cells and subcellular structures. A connection has been established for a number of serious diseases with chromosomal abnormalities.
Chromosomal disorders occur in 7 out of every thousand newborns, and they also lead to the death of the embryo (miscarriage) in the first third of pregnancy in half of all cases. If a child with chromosomal disorders is born alive, it usually suffers from severe ailments, lags behind in mental and physical development.

Biochemical method allows you to identify many hereditary human diseases associated with metabolic disorders. Anomalies of carbohydrate, amino acid, lipid and other types of metabolism are known.
So, for example, diabetes mellitus is caused by a violation of the normal activity of the pancreas - it does not release the necessary amount of the hormone insulin into the blood, resulting in an increase in blood sugar. This disorder is not caused by a single gross error in genetic information, but by a collection of small errors that collectively lead to or predispose to disease.

The population method provides information about the degree of heterozygosity and polymorphism of human populations, reveals differences in allele frequencies between different populations.

ontogenetic method. The development of normal and pathological signs is considered in the course of individual development.

mapping they use chromosomal rearrangements, which makes it possible to establish the localization of genes in a certain region of the chromosome, to determine the sequence of their location, that is, to build maps of human chromosomes.

Methods of genetics of somatic cells turned out to be more promising for mapping human genes. The essence of one of them is as follows. Cell engineering techniques allow combining 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 the fusion of protoplasts, multinucleated heterokaryotic cells are formed. Subsequently, during the fusion of the nuclei, synkarotic cells are formed, containing chromosome sets of different organisms in the nuclei. When such cells divide in vitro, hybrid cell cultures are formed. At present, cell hybrids "human × mouse", "human × rat" and many others have been obtained and cultivated.

In hybrid cells derived from different strains of different species, one of the parental sets of chromosomes tends to replicate faster than the other. Therefore, the latter gradually loses chromosomes. These processes proceed intensively, for example, in cell hybrids between mice and humans, species that differ in many biochemical markers. If, at the same time, some biochemical marker is monitored, for example, the enzyme thymidine kinase, and at the same time cytogenetic control is carried out, identifying chromosomes in clones formed after their partial loss, then, in the end, the disappearance of a chromosome can be associated simultaneously with a biochemical trait. This means that the gene encoding this trait is localized on this chromosome. Thus, the human thymidine kinase gene is located on chromosome 17.

Medical genetics - study and possible prevention of the consequences of genetic defects in humans. According to the World Health Organization, an average of three new hereditary diseases are registered annually due to the use of new diagnostic methods.
In order to imagine how often they occur, it is necessary to turn to world statistics, which say that 4-5% of newborns, as a rule, are burdened with hereditary diseases. Therefore, the study of hereditary diseases, their prevention and treatment in human genetics is one of the main tasks.
No less important are such questions as the question of what serves as a source of hereditary changes (mutations) and how to influence the further evolution of man in order to save the human race from many ailments.

Medical genetic counseling is a type of medical care for the population aimed at the prevention of hereditary diseases. It turns out in medical genetic consultations and specialized research medical institutes. The main tasks of M.-g.k. are the determination of the prognosis for future offspring in families where there is a patient with a hereditary pathology or the birth of a child with such a pathology is expected; clarification of the diagnosis of a hereditary disease using special genetic research methods; explaining in an accessible form the meaning of the medical genetic conclusion to those who have applied for advice and assistance in making the right decision regarding further family planning; promotion of medical genetic knowledge. Medical genetic counseling definition heterozygous carrier, i.e., the identification in a population of individuals who do not themselves suffer from a hereditary disease, but are heterozygous for a recessive mutation that can cause it. calculate the probability of their having a descendant - homozygous for the recessive allele.

Conditionally hereditary diseases can be divided into 3 large groups: metabolic diseases, molecular diseases (gene mutations), chromosomal diseases. Albinism, phenylketonuria, color blindness, hemophilia, Down syndrome, Shershevsky-Turner syndrome, etc. Terms " hereditary diseases" and " congenital diseases» are unequal. The term "congenital diseases" reflects only one facet of hereditary pathology - its congenital nature, i.e. manifestation of pathology already at birth. However, even congenital malformations do not always appear at birth - in children aged 1 year of life, they are detected 5 times more often than in the neonatal period. Congenital diseases can be caused not only by heredity, but also caused by non-hereditary factors (infections, chemical agents, radiation, teratogenic substances, including drugs, etc.). Many hereditary diseases (more than 50%) do not appear at birth, but can manifest many years after birth - in childhood (phosphate diabetes, some aminoacidopathy, hereditary syndromes, etc.) and even in adulthood (Huntington's chorea, myotonic dystrophy , gout, etc.).

Chromosomal and gene diseases

Gene diseases are a heterogeneous group of human hereditary diseases caused by gene mutations. Depending on the change in the protein products of the mutated genes, two groups of mutations are distinguished.

1. Qualitative changes in protein molecules - the presence of abnormal proteins (pathological hemoglobins) in patients, which is due to mutations in structural genes.

2. Quantitative changes in the content of normal protein in the cell, which is due to violations of the regulation of genes (trask-

riptional, translational and post-translational levels).

Phenotypically, gene mutations manifest themselves as hereditary metabolic diseases - fermentopathy. currently described

about 4000 hereditary metabolic diseases. The general frequency of gene diseases in populations is 2-4%.

Gene diseases are classified according to their phenotypic manifestation: diseases associated with a violation of amino acid, carbohydrate, lipid, mineral metabolism and nucleic acid metabolism,

coagulation disorders, hemoglobinopathies.

Phenylketonuria (PKU) occurs with a frequency of 1:10,000. It is inherited in an autosomal recessive manner.

Albinism occurs with a frequency of 1:5,000 - 25,000. It is inherited in an autosomal recessive manner. Tyrosinase activity is impaired.

Hemophilia is a group of hereditary diseases caused by mutation of genes, blood coagulation factors. Type of inheritance - X-linked recessive.

Sickle cell anemia is a disease caused by a mutation that results in a substitution in position 6 of the β-chain of glutamic acid (Hb A) for valine (HbS). In homozygotes for the mutant gene, erythrocytes

acquire a crescent shape, chronic hypoxia and anemia develop, hemolysis and breakdown of red blood cells (possible death).

At the core chromosomal diseases are mutations associated with a violation of ploidy, changes in the number of chromosomes, or a violation

their structures. Violation of ploidy is represented only by the triploidy syndrome (children die in the first hours or days after birth). Trisomy is the most common form of chromosomal pathology in humans.

Complete monosomy, compatible with life, is observed only on the X chromosome. In addition to complete trisomies and monosomies, partial monosomies (deletions) and partial trisomies (duplications) can be causes of human chromosomal diseases.

Down syndrome (trisomy 21 syndrome) is the most common form of chromosomal pathology in humans: 1:900. Children with Down syndrome are more often born to elderly parents (in mothers aged 41-46, the probability of having a sick child increases to 4.1%).

Various combinations of x and y chromosomes in polysomy on sex chromosomes, except for xy (norms), are combined under the general name of Klinefelter's syndrome.

X0 monosomy. Shershevsky-Turner syndrome.

Immunogenetics branch of immunology and genetics that studies the patterns of inheritance of antigenic specificity of various body tissues and the role of genetic mechanisms in the implementation of immunological processes.

The immunoglobulin genes are autosomal and codominant. The structural diversity of immunoglobulins is determined by the sequence of amino acids.

In biology, there was the principle of "one gene - one polypeptide chain", and the immutability of the genome in the ontogeny of the organism was also affirmed. However, in the case of Ig, it can be seen that several genes code for one polypeptide chain.

Immunoglobulins are controlled by three families of genes located on different chromosomes. One family encodes the synthesis of all classes of heavy chains (H), the other - the synthesis of light k-chains, the third - the synthesis of light A. chains.

Genetic aspects of oncology. The genetic apparatus of cells has a complex system for controlling cell division, growth, and differentiation. Two regulatory systems that have a cardinal effect on the process of cell proliferation have been studied.

Proto-oncogenes

Proto-oncogenes are a group of normal cell genes that have a stimulating effect on cell division processes through specific products of their expression. The transformation of a proto-oncogene into an oncogene (a gene that determines the tumor properties of cells) is one of the mechanisms for the emergence of tumor cells. This can occur as a result of a mutation of a proto-oncogene with a change in the structure of a specific gene expression product, or an increase in the expression level of a proto-oncogene when its regulatory sequence is mutated (point mutation) or when a gene is transferred to an actively transcribed region of the chromosome (chromosomal aberrations).

Although the number of products encoded by oncogenes, oncoproteins, is large, and the mechanisms by which they carry out their action are different, all these mechanisms can be grouped into three main categories:

Phosphorylation of proteins at serine, threonine, or tyrosine residues by protein kinases. As a result, the functional properties of the phosphorylation target protein change.

Signaling via GTP-binding proteins, as is the case for the RAS oncoprotein.

Transcriptional control, as is the case for the oncoproteins FOS, MYC, and others.

But we must keep in mind that our understanding of the mechanisms of tumor transformation is constantly changing in the course of accumulating more and more new information. As a result, proteins such as cadherins, which carry out cell adhesion, and translation factors, and cytoskeletal proteins and beta-catenin, which is an intracellular polypeptide that interacts with cadherin in one of the signal transduction pathways from the cell surface to the nucleus, are identified as oncoproteins. The list will surely grow. Oncogenesis is associated, in particular, with the inability of the stem cell to differentiate, i.e. to turn into a certain specific cell formed to perform certain tasks. It is becoming increasingly clear that it can be caused by a slight imbalance in the levels of common regulators required at various stages of cellular existence.

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

Goals

The developed methods for studying 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 how 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:

genetic foundations of the physiological and anatomical characteristics of tissues, organs, the organism as a whole;
causes of predispositions, abilities and talents in a certain field of activity;
patterns of distribution of genes between descendants;
causes and ways to prevent genetic diseases;
genetic conditioning of the work of memory, thinking, emotions;
mechanisms of beneficial and harmful mutations.

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

Methods

Human-related research faces several challenges of a biological and socio-ethical nature.
Biological issues include:

work with a large number of chromosomes;
late puberty of a person;
a long period of pregnancy - the impossibility of obtaining offspring in a short time;
long generational change (for 20-25 years);
low fertility - one or two offspring in one pregnancy.

Rice. 1. Human karyotype.

The social problems of studying human heredity are:

the impossibility of experimental crossing - one cannot use human life for scientific purposes;
the difficulty of creating equal environmental conditions for observations - each person is unique due to social upbringing and character traits, therefore it is almost impossible to equate even two lives.

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

What have we learned?

From the 10th grade lesson, we learned about the features and goals of human genetics. We briefly reviewed the main methods for studying human genetic information. With the help of study methods, it is possible to identify not only phenotypic signs and deviations from the norm in the future generation, but also a predisposition to various genetic diseases, as well as predict risks.

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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 a population
Biochemical	Detects malfunctions of the genes that are responsible for metabolism	Identification of predisposition to various metabolic diseases - diabetes mellitus, phenylketonuria, lactase deficiency
Dermatoglyphic	Studying the relief of the skin on the fingers (dactyloscopy), palms (palmoscopy), soles of the feet (plantoscopy)	Used to determine personality, in the diagnosis of hereditary diseases, in forensic medicine
Gemini	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 particular symptom or disease (schizophrenia, epilepsy)
Genealogical	The study of 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 the norm and in the presence of pathology	Study of chromosomal diseases - Down syndrome, Klinefelter syndrome, Turner-Shereshevsky syndrome, cat's cry syndrome