For genetic research, a person is an inconvenient object, since in a person: experimental crossing is impossible; a large number of chromosomes; puberty comes late; a small number of descendants in each family; equalization of living conditions for offspring is impossible.

A number of research methods are used in human genetics.

genealogical method

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 studied trait; 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. So, according to the autosomal dominant type, 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, 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 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; - carrier woman

twin method

1 - monozygotic twins; 2 - dizygotic twins.

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, %
	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.

Cytogenetic method

Based on the study of human chromosomes in normal and pathological conditions. Normally, a human karyotype includes 46 chromosomes - 22 pairs of autosomes and two sex chromosomes. The use of this method made it possible to identify a group of diseases associated either with a change in the number of chromosomes or with changes in their structure. Such diseases are called chromosomal.

Blood lymphocytes are the most common material for karyotypic analysis. Blood is taken in adults from a vein, in newborns - from a finger, earlobe or heel. Lymphocytes are cultivated in a special nutrient medium, which, in particular, contains substances that “force” lymphocytes to intensively divide by mitosis. After some time, colchicine is added to the cell culture. Colchicine stops mitosis at the metaphase level. It is during metaphase that the chromosomes are most condensed. Next, the cells are transferred to glass slides, dried and stained with various dyes. Coloring can be a) routine (chromosomes stain evenly), b) differential (chromosomes acquire transverse striation, with each chromosome having an individual pattern). Routine staining allows you to identify genomic mutations, determine the group belonging of the chromosome, and find out in which group the number of chromosomes has changed. Differential staining allows you to identify chromosomal mutations, determine the chromosome to the number, find out the type of chromosomal mutation.

In cases where it is necessary to conduct a karyotypic analysis of the fetus, cells of the amniotic (amniotic) fluid are taken for cultivation - a mixture of fibroblast-like and epithelial cells.

Chromosomal diseases include: Klinefelter syndrome, Turner-Shereshevsky syndrome, Down syndrome, Patau syndrome, Edwards syndrome and others.

Patients with Klinefelter's syndrome (47, XXY) are always male. They are characterized by underdevelopment of the sex glands, degeneration of the seminiferous tubules, often mental retardation, high growth (due to disproportionately long legs).

Turner-Shereshevsky syndrome (45, X0) is observed in women. It manifests itself in slowing down puberty, underdevelopment of the gonads, amenorrhea (absence of menstruation), infertility. Women with Turner-Shereshevsky syndrome are small in stature, the body is disproportionate - the upper body is more developed, the shoulders are wide, the pelvis is narrow - the lower limbs are shortened, the neck is short with folds, the “Mongoloid” eye shape and a number of other signs.

Down syndrome is one of the most common chromosomal diseases. It develops as a result of trisomy on chromosome 21 (47; 21, 21, 21). The disease is easily diagnosed, as it has a number of characteristic features: shortened limbs, a small skull, a flat, wide nose, narrow palpebral fissures with an oblique incision, the presence of a fold of the upper eyelid, and mental retardation. Violations of the structure of internal organs are often observed.

Chromosomal diseases also occur as a result of changes in the chromosomes themselves. Yes, deletion R-arm of autosome number 5 leads to the development of the "cat's cry" syndrome. In children with this syndrome, the structure of the larynx is disturbed, and in early childhood they have a kind of “meowing” voice timbre. In addition, there is a retardation of psychomotor development and dementia.

Most often, chromosomal diseases are the result of mutations that have occurred in the germ cells of one of the parents.

Biochemical method

Allows you to detect metabolic disorders caused by changes in genes and, as a result, changes in the activity of various enzymes. Hereditary metabolic diseases are divided into diseases of carbohydrate metabolism (diabetes mellitus), metabolism of amino acids, lipids, minerals, etc.

Phenylketonuria refers to diseases of amino acid metabolism. The conversion of the essential amino acid phenylalanine to tyrosine is blocked, while phenylalanine is converted to phenylpyruvic acid, which is excreted in the urine. The disease leads to the rapid development of dementia in children. Early diagnosis and diet can stop the development of the disease.

Population-statistical method

It is a method of studying the distribution of hereditary traits (inherited diseases) in populations. An essential point when using this method is the statistical processing of the obtained data. Under population understand the totality of individuals of the same species, living in a certain territory for a long time, freely interbreeding with each other, having a common origin, a certain genetic structure and, to one degree or another, isolated from other such populations of individuals of a given species. A population is not only a form of existence of a species, but also a unit of evolution, since the basis of microevolutionary processes culminating in the formation of a species are genetic transformations in populations.

The study of the genetic structure of populations deals with a special section of genetics - population genetics. In humans, three types of populations are distinguished: 1) panmictic, 2) demes, 3) isolates, which differ from each other in number, frequency of intra-group marriages, the proportion of immigrants, and population growth. The population of a large city corresponds to the panmictic population. The genetic characteristics of any population includes the following indicators: 1) gene pool(the totality of genotypes of all individuals of a population), 2) gene frequencies, 3) genotype frequencies, 4) phenotype frequencies, marriage system, 5) factors that change gene frequencies.

To determine the frequencies of occurrence of certain genes and genotypes, hardy-weinberg law.

Hardy-Weinberg law

In an ideal population, from generation to generation, a strictly defined ratio of frequencies of dominant and recessive genes (1), as well as the ratio of frequencies of genotypic classes of individuals (2) is preserved.

p + q = 1, (1)
R 2 + 2pq + q 2 = 1, (2)

where p— frequency of occurrence of the dominant gene A; q- the frequency of occurrence of the recessive gene a; R 2 - the frequency of occurrence of homozygotes for the dominant AA; 2 pq- frequency of occurrence of Aa heterozygotes; q 2 - the frequency of occurrence of homozygotes for the recessive aa.

The ideal population is a sufficiently large, panmictic (panmixia - free crossing) population, in which there is no mutation process, natural selection and other factors that disturb the balance of genes. It is clear that ideal populations do not exist in nature; in real populations, the Hardy-Weinberg law is used with amendments.

The Hardy-Weinberg law, in particular, is used to roughly count the carriers of recessive genes for hereditary diseases. For example, phenylketonuria is known to occur at a rate of 1:10,000 in a given population. Phenylketonuria is inherited in an autosomal recessive manner, therefore, patients with phenylketonuria have the aa genotype, that is q 2 = 0.0001. From here: q = 0,01; p= 1 - 0.01 = 0.99. Carriers of the recessive gene have the Aa genotype, that is, they are heterozygotes. The frequency of occurrence of heterozygotes (2 pq) is 2 0.99 0.01 ≈ 0.02. Conclusion: in this population, about 2% of the population are carriers of the phenylketonuria gene. At the same time, you can calculate the frequency of occurrence of homozygotes for the dominant (AA): p 2 = 0.992, just under 98%.

A change in the balance of genotypes and alleles in a panmictic population occurs under the influence of constantly acting factors, which include: the mutation process, population waves, isolation, natural selection, gene drift, emigration, immigration, inbreeding. It is thanks to these phenomena that an elementary evolutionary phenomenon arises - a change in the genetic composition of a population, which is the initial stage in the process of speciation.

Human genetics is one of the most intensively developing branches of science. It is the theoretical basis of medicine, reveals the biological basis of hereditary diseases. Knowing the genetic nature of diseases allows you to make an accurate diagnosis in time and carry out the necessary treatment.

Go to lectures №21"Variability"

1. Genealogical

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.

As a method of studying human genetics, the genealogical method began to be used only from the beginning of the 20th century, when it became clear that the analysis of pedigrees in which the transmission of some trait (disease) from generation to generation can be replaced by the hybridological method, which is actually inapplicable to humans.

When compiling pedigrees, the source is a person - a proband, whose pedigree is being studied. Usually this is either a patient, or a carrier of a certain trait, the inheritance of which needs to be studied.

Proband - the person from whom the compilation of a pedigree begins during genealogical analysis.

Sibs - one of the children born to the same parents, in relation to other children (for example, a brother or sister).

2. Gemini

This method consists in studying the patterns of inheritance of traits in pairs of identical and dizygotic twins. It was proposed in 1875 by Galton initially to assess the role of heredity and environment in the development of a person's mental properties. At present, this method is widely used in the study of heredity and variability in humans to determine the relative role of heredity and environment in the formation of various signs, both normal and pathological. It 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. Monozygotic Twins , developing from a single fertilized egg, are genetically identical, as they have 100% of common genes. Therefore, among monozygotic twins there is a high percentage of concordant steam, in which the trait develops in both twins. Comparison of monozygotic twins brought up in different conditions of the postembryonic period 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. On the contrary, the preservation of similarity between twins, despite the differences in the conditions of their existence, indicates the hereditary conditionality of the trait.

3. Population-statistical

With the help of the population-statistical method, hereditary traits are studied in large groups of the population, in one or several generations. An essential point when using this method is the statistical processing of the obtained data. This method can be used to calculate 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 studying the mutation process, the role of heredity and environment in the formation of human phenotypic polymorphism according to normal traits, as well as in the occurrence of diseases, especially with hereditary predisposition. This method is also used to elucidate the significance of genetic factors in anthropogenesis, in particular in racial formation.

4. 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. Probably, 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 used mainly in forensic medicine.

5. 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 amount, 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.

6. 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 conjunction 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.

7.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.

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.

8.Simulation 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, intoxications, 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.

9.Immunogenetic

The immunological (serological) method includes the study of blood serum, as well as other biological substrates for the detection of antibodies and antigens.
There are serological reactions and immunological methods using physical and chemical labels. Serological reactions are based on the interaction of antibodies with antigens and registration of accompanying phenomena (agglutination, precipitation, lysis). In immunological methods, physical and chemical labels are used, which are included in the formed antigen-antibody complex, allowing the formation of this complex to be recorded.
Classical serodiagnosis is based on the determination of antibodies to an identified or suspected pathogen. A positive result of the reaction indicates the presence in the test blood serum of antibodies to the antigens of the pathogen, a negative result indicates the absence of such.
Serological reactions are semi-quantitative and allow to determine the antibody titer, i.e. the maximum dilution of the test serum, in which a positive result is still observed.
The detection of antibodies to the causative agent of a number of infectious diseases in the studied blood serum is not enough to make a diagnosis, since it may reflect the presence of post-infectious or post-vaccination immunity. That is why paired sera are examined - taken in the first days of the disease and after 7-10 days. In this case, the increase in antibody titer is assessed. A diagnostically significant increase in antibody titer in the studied blood serum relative to the initial level is 4 times or more. This phenomenon is called seroconversion.
In exotic infectious diseases, as well as in hepatitis, HIV infection and some other diseases, the very fact of detecting antibodies indicates that the patient is infected and has diagnostic value.

Sections: Biology

Lesson Objectives:

• To expand and deepen students' knowledge on the topic - features of the study of human genetics,
• To form knowledge about the main methods of studying human heredity; to teach to determine the main types of inheritance in humans.
• Show the importance of genetic knowledge for modern man; the role of mutagens and the appearance of mutations in humans.

Equipment: tables on general biology, presentation “Human genetics. Methods for studying human heredity ", on the tables of the study tables" Examples of pedigrees, "Inheritance of various traits in humans"

DURING THE CLASSES

1. Organizational moment

2. Introductory speech of the teacher. Knowledge update

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. The purpose of medical genetics is to develop methods for diagnosing, treating and preventing human hereditary pathology.

3. Learning new material

The objectives of human genetics are:

• determination of the complete nucleotide sequence of the DNA of the human genome, localization of genes and creation of their bank;
• early diagnosis of hereditary pathology by improving the methods of prenatal and express diagnostics;
• widespread introduction of medical genetic counseling;
• development of methods for gene therapy of hereditary diseases based on genetic engineering;
• identification of genetically dangerous environmental factors and development of methods for their neutralization.

Man as a specific object of genetics

The study of human genetics is associated with great difficulties:

• complex karyotype - many chromosomes and linkage groups;
• late puberty and a rare change of generations;
• a small number of descendants;
• impossibility of experimentation
• the impossibility of creating the same living conditions.

Despite these difficulties, human genetics is currently better understood than the genetics of many other organisms (for example, mammals) due to the needs of medicine and a variety of modern research methods.
During the lesson, students are asked to complete the table:

Table 1. Methods for studying human heredity

method	its essence and meaning

Methods for the study of human genetics

The author of many methods for studying human genetics is F. Galton
Sir Francis Galton(Eng. Francis Galton; February 16, 1822 - January 17, 1911) - English explorer, geographer, anthropologist and psychologist; founder of differential psychology and psychometrics. Born in Birmingham, England.
Galton was the cousin of Charles Darwin's grandfather, Erasmus Darwin.

A. Genealogical method

The oldest method of human genetics is genealogical analysis, or the method of analyzing pedigrees. The essence of the method is the compilation of a pedigree and its subsequent analysis. It was introduced in 1865. F. Galton.
Pedigree analysis is used to identify dominant, semi-dominant and recessive traits, chromosome mapping (i.e., to establish whether the gene encoding a given trait belongs to a specific linkage group, linkage to X or Y chromosomes), to study the mutation process (especially in cases when it is necessary to distinguish newly emerged mutations from those that are familial, i.e., originated in previous generations).
Polydactyly (an increased number of fingers), freckles, early baldness, fused fingers, eye cataracts, brittle bones, and many others are inherited in an autosomal dominant manner.
Albinism, red hair, susceptibility to polio, diabetes mellitus, congenital deafness are inherited in an autosomal recessive manner.
A number of traits are inherited, sex-linked: X-linked inheritance - hemophilia, color blindness; Y-linked - hypertrichosis (increased hairiness of the auricle), membranes between the fingers.
The genealogical method is widely used to solve both scientific and applied problems. It allows you to identify the hereditary nature of the trait and determine the type of inheritance. The genealogical method underlies medical genetic counseling.

Students are invited to solve the problem: determine the type of inheritance according to the pedigree

Task 1. In the family pedigree, there is a trait - "gray lock of hair", which is inherited as dominant (Fig. 1). Determine the genotypes of the original parents. What descendants are expected from the marriage of cousins ​​and brothers a) 1 and 5; b) 2 and 6?.

B. Twin method

This method of studying human genetics was also introduced into medical practice by F. Galton in 1876. It makes it possible to determine the contribution of genetic (hereditary) and environmental factors (climate, nutrition, education, upbringing, etc.) in the development of specific signs or diseases in humans.
It is known that in humans there are two categories of twins. In some cases, not one egg is fertilized, but two. In this case, children of the same or different sexes are born, similar to each other as brothers and sisters who are not twins. But sometimes one egg gives rise to two (three, four) embryos. Then identical twins are obtained, which always belong to the same sex and show a striking resemblance to each other. This is understandable, since they have the same genotype, and the differences between them are due solely to the influence of the environment in the development of the physical and mental properties of a person.

B. Biochemical method

For the first time, biochemical methods began to be used for the diagnosis of gene diseases as early as the beginning of the 20th century. Over the past 30 years, they have been widely used in the search for new forms of mutant alleles. With their help, 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 such diseases are diseases associated with defective enzymes, structural, transport or other proteins.
One of the most common diseases of carbohydrate metabolism is diabetes mellitus. This disease is associated with a deficiency of the hormone insulin, which leads to a disruption in the formation of glycogen and an increase in blood glucose levels.
Phenylketonuria refers to diseases of amino acid metabolism. At the same time, the conversion of the essential amino acid phenylalanine to tyrosine is blocked, and phenylalanine is converted to phenylpyruvic acid, which is excreted in the urine. The disease leads to the rapid development of dementia in children. Early diagnosis and diet can stop the development of the disease.

D. Cytogenetic method

The basis of the method is the microscopic study of human chromosomes. Cytogenetic studies have been widely used since the early 20s of the twentieth century to study the morphology and count of human chromosomes, the cultivation of leukocytes to obtain metaphase plates
The development of modern human cytogenetics is associated with the names of cytologists D. Tio and A. Levan. In 1956 They were the first to establish that a person has 46, and not 48, as previously thought, chromosomes. This event marked the beginning of a broad study of human mitotic and meiotic chromosomes.

In 1960 The first international classification of human chromosomes was developed in Denver (USA). It was based on the size of the chromosomes and the position of the primary constriction - the centromere.

Each pair of chromosomes is designated by a serial number from 1 to 23, the sex chromosomes are separately identified - X and Y. Women have two X chromosomes, men have X and Y chromosomes

The use of this method made it possible to identify a group of diseases associated with a change in the number of chromosomes, or with a change in their structure. Such diseases are called chromosomal, they include: disorders in somatic chromosomes.

"Human Chromosomal Diseases"

Student messages:

To date, more than 2 thousand human hereditary diseases have been registered.
According to the World Health Organization, thanks to the use of new diagnostic methods, an average of three new hereditary diseases are registered annually, which occur in the practice of a doctor of any specialty: therapist, surgeon, neuropathologist, obstetrician-gynecologist, pediatrician, endocrinologist, etc. Diseases that do not have absolutely nothing to do with heredity, practically does not exist. The course of various diseases (viral, bacterial, fungal infections, and even injuries) and recovery after them to some extent depend on the hereditary immunological, physiological, behavioral and mental characteristics of the individual.

Chromosomal diseases. This type of hereditary disease is associated with a change in the number or structure of chromosomes. The frequency of chromosomal abnormalities in newborns is from 0.6 to 1%, and at the stage of 8-12 weeks, about 3% of embryos have them. Among spontaneous miscarriages, the frequency of chromosomal abnormalities is approximately 30%, and in the early stages (up to two months) - 50% and above.
In humans, all types of chromosomal and genomic mutations have been described, including aneuploidy, which can be of two types - monosomy and polysomy. Monosomy is especially severe.
Whole-body monosomy has been described for the X chromosome. This is Shereshevsky-Turner syndrome(44 + X), manifested in women who are characterized by pathological changes in physique (short stature, short neck, with folds, "Mongoloid" eye section, narrow pelvis, lower limbs), disorders in the development of the reproductive system (absence of most female secondary sexual signs), mental disability. The frequency of occurrence of this anomaly is 1:4000-5000.
Women - trisomics (44 + XXX), as a rule, are distinguished by violations of sexual, physical and mental development, although in some patients these signs may not appear. Cases of fertility of such women are known. The frequency of the syndrome is 1:1000.

Men with Klinefelter syndrome (44+ XXY) are characterized by a violation of the development and activity of the gonads, eunuchoid body type (narrower than the pelvis, shoulders, body hair and fat deposition on the body according to the female type, arms and legs elongated compared to the body). Hence the higher growth. These signs, combined with some mental retardation, appear in a relatively normal boy from the time of puberty.
Klinefelter's syndrome is observed with polysomy not only on the X chromosome (XXX XXXY, XXXXY), but also on the Y chromosome (XYY. XXYY. XXYYY). The frequency of the syndrome is 1:1000.
Of the autosomal diseases, trisomy on the 21st chromosome, or down syndrome. According to various authors, the birth rate of children with Down syndrome is 1:500-700 newborns, and over the past decades, the frequency of trisomy-21 has increased.
Typical signs of patients with Down syndrome: a small nose with a wide flat bridge of the nose, slanting eyes with an epicanthus - an overhanging fold over the upper eyelid, deformed small auricles, a half-open mouth, short stature, mental retardation. About half of the patients have heart disease and large vessels.
There is a direct relationship between the risk of having children with Down syndrome and the age of the mother. It has been established that 22-40% of children with this disease are born to mothers over 40 years old (2-3% of women of childbearing age).

Patau Syndrome- the syndrome is based on nondisjunction on the 13th pair of chromosomes. In the karyotype of the patient, 47 chromosomes are observed with an extra chromosome - 13.

Syndrome "cat's cry"

Cytologically, in all patients, a shortening (deletion) of approximately one third of the short arm of one of the chromosome 5 homologues is detected.
Here, only some examples of human gene and chromosomal diseases are considered, which, however, give a certain idea of ​​the complexity and fragility of its genetic organization.

Violation of the number of sex chromosomes.

Diseases caused by a change in the number of sex chromosomes are much milder than autosomal anomalies. They are usually accompanied by mental decline and sterility. There are various syndromes associated with a violation of the number of heterosomes.

Genetics and medicine Medical genetic counseling

Currently, the greatest attention is paid to measures to prevent the birth of children with hereditary pathology.
The main way to prevent hereditary diseases is their prevention. First of all, its services should be used by persons entering into marriage who have genetically disadvantaged relatives. Genetic counseling is obligatory upon marriage of relatives, persons over 30-40 years old, as well as those working in production with harmful working conditions. Doctors and geneticists will be able to determine the degree of risk of the birth of genetically defective offspring and ensure control over the child during its intrauterine development. It should be noted that smoking, alcohol and drug use by the mother or father of the unborn child dramatically increase the likelihood of the baby being born with severe hereditary ailments.

The importance of human genetics, a detailed acquaintance with the pedigrees of people seeking advice, allows the geneticist to assess the degree of risk in each case.
Thus, the current trends in human genetics is an active counteraction to adverse factors that cause hereditary anomalies based on the knowledge of genetic patterns.

4. Consolidation of acquired knowledge

1. Checking the completed table No. 1
2. Verification of task #1
3. As a consolidation of the acquired knowledge, students are offered a test

1) What is the name of the method, the essence of which is the crossing of parental forms that differ in a number of characteristics, the analysis of their manifestation in a number of generations?

A) hybrid
B) cytogenetic
B) twins
D) biochemical

2) By what method is the influence of the genotype and environment on the development of the child revealed?

A) genealogy
B) twin
B) cytogenetic
D) hybridological

3) Chromosome sets of healthy and sick people are studied using the method

A) genealogy
B) cytogenetic
B) twin
D) hybridological

4) Chromosome sets of healthy and sick people are studied using the method

A) genealogy
B) cytogenetic
B) twin
D) hybridological

5) What variability causes the difference in the phenotypes of identical twins

A) genetic
B) genomic
B) modification
D) mutational

A) can be of different sexes
B) always the same sex
B) have the same weight
D) they are the same size

7) Using the genealogical method, you can find out

A) the nature of the change in genes
B) the influence of education on the development of a person's mental characteristics
C) patterns of inheritance of traits in humans
D) the nature of the change in chromosomes

8) The method of studying human heredity, which is based on the study of the number of chromosomes, the features of their structure, is called

A) genealogy
B) twin
B) hybridological
D) cytogenetic

5. Summing up the lesson. Homework

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 is the 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 medicines, 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 tissues of the body 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.

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:

1. 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.

1. 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.

1. 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.

1. 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.

1. 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

1. 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

1. sick not in every generation
2. men and women are affected equally
3. inheritance is predominantly horizontal
4. 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

1. sick not in every generation
2. healthy parents have a sick child
3. predominantly men are affected
4. inheritance is mostly horizontal
5. 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

1. patients in all generations
2. only men get sick
3. a sick father has sick all his sons
4. 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 traits 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.

1. 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 in 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.