The role of genetics for practical medicine. The value of genetics for medicine and public health. Familial nature of the disease

The importance of genetics for medicine and health care

The subject and tasks of human genetics. Human genetics, or medical genetics, studies the phenomena of heredity and variability in various populations of people, the features of the manifestation and development of normal (physical, creative, intellectual abilities) and pathological signs, the dependence of diseases on genetic predetermination and environmental conditions, including social conditions. life. The formation of medical genetics began in the 1930s. XX century, when facts began to appear confirming that the inheritance of traits in humans obeys the same patterns as in other living organisms.

The task of medical genetics is to identify, study, prevent and treat hereditary diseases, as well as to develop ways to prevent the harmful effects of environmental factors on human heredity.

Methods for studying human heredity. When studying the heredity and variability of a person, the following methods are used: genealogical, twin, cytogenetic, biochemical, dermatoglyphic, hybridization of somatic cells, modeling, etc.

The genealogical method allows you to find out family ties and trace the inheritance of normal or pathological traits among close and distant relatives in a given family based on the compilation of a pedigree - genealogy. If there are pedigrees, then, using summary data for several families, it is possible to determine the type of inheritance of a trait - dominant or recessive, sex-linked or autosomal, as well as its monogenicity or polygenicity. The genealogical method has proven the inheritance of many diseases, such as diabetes, schizophrenia, hemophilia, etc.

The genealogical method is used for the diagnosis of hereditary diseases and medical genetic counseling; it allows for genetic prophylaxis (prevention of the birth of a sick child) and early prevention of hereditary diseases.

The twin method consists in studying the development of traits in twins. It allows you to determine the role of the genotype in the inheritance of complex traits, as well as to evaluate the influence of such factors as upbringing, training, etc.

It is known that in humans, twins are identical (monozygous) and fraternal (dizygotic). Identical, or identical, twins develop from one egg fertilized by one sperm. They are always the same sex and strikingly similar to each other, as they have the same genotype. In addition, they have the same blood type, the same fingerprints and handwriting, even their parents confuse them and do not distinguish them by the smell of a dog. Only identical twins are 100% successful in organ transplants, since they have the same set of proteins and the transplanted tissues are not rejected. The proportion of identical twins in humans is about 35--38% of their total number.

Fraternal, or dizygotic, twins develop from two different eggs, simultaneously fertilized by different spermatozoa. Dizygotic twins can be of the same or different sexes, and from a genetic point of view, they are no more similar than ordinary brothers and sisters.

The study of identical twins throughout their lives, especially if they live in different socio-economic and natural-climatic conditions, is interesting because the differences between them in the development of physical and mental properties are explained not by different genotypes, but by the influence of environmental conditions.

The cytogenetic method is based on a microscopic examination of the structure of chromosomes in healthy and sick people. Cytogenetic control is used in the diagnosis of a number of hereditary diseases associated with aneuploidy and various chromosomal rearrangements. It also makes it possible to study tissue aging on the basis of studies of the age-related dynamics of cell structure, to establish the mutagenic effect of environmental factors on humans, etc.

In recent years, the cytogenetic method has gained great importance in connection with the possibilities of human genetic analysis, which were opened by the hybridization of somatic cells in culture. Obtaining interspecific hybrids of cells (for example, a human and a mouse) makes it possible to get much closer to solving problems associated with the impossibility of directed crosses, localize a gene on a certain chromosome, establish a linkage group for a number of characters, etc. Combining the genealogical method with the cytogenetic method, and also with the latest methods of genetic engineering has greatly accelerated the process of gene mapping in humans.

Biochemical methods for studying human heredity help to detect a number of metabolic diseases (carbohydrate, amino acid, lipid, etc.) using, for example, the study of biological fluids (blood, urine, amniotic fluid) by qualitative or quantitative analysis. The cause of these diseases is a change in the activity of certain enzymes.

With the help of biochemical methods, about 500 molecular diseases have been discovered, which are the result of the manifestation of mutant genes. With various types of diseases, it is possible either to determine the abnormal protein-enzyme itself, or to establish intermediate metabolic products. According to the results of biochemical analyzes, it is possible to diagnose the disease and determine the methods of treatment. Early diagnosis and the use of various diets at the first stages of postembryonic development can cure some diseases or at least alleviate the condition of patients with defective enzyme systems.

Like any other discipline, modern human genetics uses the methods of related sciences: physiology, molecular biology, genetic engineering, biological and mathematical modeling, etc. A significant place in solving the problems of medical genetics is occupied by the ontogenetic method, which allows us to consider the development of normal and pathological traits in the course of individual development.

Human hereditary diseases, their treatment and prevention. To date, more than 2,000 hereditary human diseases have been registered, and most of them are associated with mental disorders. 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.

Conditionally hereditary diseases can be divided into three large groups: metabolic diseases, molecular diseases, which are usually caused by gene mutations, and chromosomal diseases.

Gene mutations and metabolic disorders. Gene mutations can be expressed in an increase or decrease in the activity of certain enzymes, up to their absence. Phenotypically, such mutations manifest themselves as hereditary metabolic diseases, which are determined by the absence or excess of the product of the corresponding biochemical reaction.

Gene mutations are classified according to their phenotypic manifestation, i.e., as diseases associated with impaired amino acid, carbohydrate, lipid, mineral metabolism, and nucleic acid metabolism.

An example of a violation of amino acid metabolism is albinism, a relatively harmless disease that occurs in Western Europe with a frequency of 1:25,000. The cause of the disease is a defect in the tyrosinase enzyme, as a result of which the conversion of tyrosine to melanin is blocked. Albinos have milky skin, very fair hair, and no pigment in the iris. They have an increased sensitivity to sunlight, which causes inflammatory skin diseases in them.

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.

A number of pathological signs (hypertension, atherosclerosis, gout, etc.) are determined not by one, but by several genes (the phenomenon of polymerization). These are diseases with a hereditary predisposition, which are more dependent on environmental conditions: under favorable conditions, such diseases may not manifest themselves.

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 the Shereshevsky-Turner syndrome (44 + X), which manifests itself in women who are characterized by pathological changes in physique (short stature, short neck), disorders in the development of the reproductive system (absence of most female secondary sexual characteristics), mental limitation. The frequency of occurrence of this anomaly is 1:4000-5000.

Trisomic women (44+XXX), as a rule, are characterized by disorders 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's syndrome (44+XXY) are characterized by impaired 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, is the most studied. 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's 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).

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.

The main way to prevent hereditary diseases is their prevention. To this end, in many countries of the world, including Belarus, there is a network of institutions that provide medical genetic counseling to the population. 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 having a baby with severe hereditary ailments.

In the case of the birth of a sick child, sometimes its medication, dietary and hormonal treatment is possible. Poliomyelitis can serve as a clear example confirming the possibilities of medicine in the fight against hereditary diseases. This disease is characterized by hereditary predisposition, but the direct cause of the disease is a viral infection. Carrying out mass immunization against the causative agent of the disease made it possible to save all children who are hereditarily predisposed to it from the severe consequences of the disease. Dietary and hormonal treatment has been successfully used in the treatment of phenylketonuria, diabetes mellitus and other diseases.

Lecture: The value of genetics for medicine

human genetics- This is one of the subsections of genetics, within the framework of which studies are carried out on the patterns and mechanisms of variability and inheritance in humans.

This science is in close connection with anthropology and medicine. It is subdivided into:

anthropogenetics is a science that studies the heredity and variability of traits that are within the normal range;

medical genetics, engaged in the study of pathological changes in the genome and the prevention of their occurrence.

Clinical (medical) genetics, in particular, studies:

features of the manifestation of pathological and normal signs;

the likelihood of chronic diseases due to genetic predisposition and the influence of the external environment.

Its main tasks are the treatment of diseases of a hereditary nature, their study, prevention, detection, and also the determination of ways to prevent the impact of mutagenic factors on the human genome.

Statistics show that in human populations the frequency of diseases of a genetic nature is 2-4%. These include various metabolic disorders, and mutations also cause incorrect development and dysfunction of various organs and their systems. For example, altered genes cause hereditary deafness, six-fingeredness, optic nerve atrophy, and others.

With a defect in the gene that encodes the structure of an enzyme that can convert phenylalanine to tyrosine, phenylketonuria disease occurs. At the same time, phenylalanine accumulating in the body turns into a variety of toxins that have a negative effect on the child's nervous system. There are convulsive seizures, impaired reflexes, weakening of mental development. Its frequency is 1:8000.

Chromosomal diseases are known, such as Down's syndrome, X-chromosome polysomy in women, and others that occur as a result of a violation of chromosome divergence during the formation of gametes. It is diagnosed in 1 in 700 babies.
Many chromosomal disorders are so severe that children, if they are born, have numerous malformations and die at an early age.

Mutagenic factors of gene disorders

The cause of gene disorders are mutagenic factors, which are divided into physical, chemical and biological.

Physical. These include various types of radiation - solar ultraviolet, radioactive, its other short-wave forms, as well as extremely high or very low temperatures.

Chemical. This is the most common cause of genomic disorders. They may be:

nitrates and others used as fertilizers;

reactive oxygen species - including peroxide;

agricultural poisons;

some of the food additives (cyclamates, etc.);

oil products;

medicines.

As well as many types of chemicals used uncontrollably in cosmetics and everyday life.

Biological. These are various biological substances that enter or are synthesized in the body:

some viruses and their toxins (influenza, rubella, measles viruses);

oxidized lipids and other metabolic products not excreted from the body;

antigens of various microorganisms.

Chemically active substances-mutagens can form complex compounds with DNA. Such DNA, “hung with” foreign molecules, not only cannot take part in transcription and replication, it changes, reacting with aggressive substances, loses pieces of its structure, which leads to serious violations of the genetic apparatus.

Currently, active research is being carried out in the field of genetic medicine. Even compared to 20 years ago, various methods for diagnosing genetic disorders of the fetus in the early stages of pregnancy have been developed and put into practice, and various comprehensive analyzes are being carried out. Work is underway to sequence (decode) the human genome.

The research results make it possible to develop new standards for various industries and agriculture that limit the use of chemical compounds that can cause mutational changes.

The environment is constantly monitored for various parameters.

The subject and tasks of human genetics. Human genetics, or medical genetics, studies the phenomena of heredity and variability in various populations of people, the features of the manifestation and development of normal (physical, creative, intellectual abilities) and pathological signs, the dependence of diseases on genetic predetermination and environmental conditions, including social conditions. life. The formation of medical genetics began in the 1930s. XX century, when facts began to appear confirming that the inheritance of traits in humans obeys the same patterns as in other living organisms.

The task of medical genetics is to identify, study, prevent and treat hereditary diseases, as well as to develop ways to prevent the harmful effects of environmental factors on human heredity.

Methods for studying human heredity. When studying the heredity and variability of a person, the following methods are used: genealogical, twin, cytogenetic, biochemical, dermatoglyphic, hybridization of somatic cells, modeling, etc.

The genealogical method allows you to find out family ties and trace the inheritance of normal or pathological traits among close and distant relatives in a given family based on the compilation of a pedigree - genealogy. If there are pedigrees, then, using summary data for several families, it is possible to determine the type of inheritance of a trait - dominant or recessive, sex-linked or autosomal, as well as its monogenicity or polygenicity. The genealogical method has proven the inheritance of many diseases, such as diabetes, schizophrenia, hemophilia, etc.

The genealogical method is used for the diagnosis of hereditary diseases and medical genetic counseling; it allows for genetic prophylaxis (prevention of the birth of a sick child) and early prevention of hereditary diseases.

The twin method consists in studying the development of traits in twins. It allows you to determine the role of the genotype in the inheritance of complex traits, as well as to evaluate the influence of such factors as upbringing, training, etc.

It is known that in humans, twins are identical (monozygous) and fraternal (dizygotic). Identical, or identical, twins develop from one egg fertilized by one sperm. They are always the same sex and strikingly similar to each other, as they have the same genotype. In addition, they have the same blood type, the same fingerprints and handwriting, even their parents confuse them and do not distinguish them by the smell of a dog. Only identical twins are 100% successful in organ transplants, since they have the same set of proteins and the transplanted tissues are not rejected. The proportion of identical twins in humans is about 35-38% of their total number.

Fraternal, or dizygotic, twins develop from two different eggs, simultaneously fertilized by different spermatozoa. Dizygotic twins can be of the same or different sexes, and from a genetic point of view, they are no more similar than ordinary brothers and sisters.

The study of identical twins throughout their lives, especially if they live in different socio-economic and natural-climatic conditions, is interesting because the differences between them in the development of physical and mental properties are explained not by different genotypes, but by the influence of environmental conditions.

The cytogenetic method is based on a microscopic examination of the structure of chromosomes in healthy and sick people. Cytogenetic control is used in the diagnosis of a number of hereditary diseases associated with aneuploidy and various chromosomal rearrangements. It also makes it possible to study tissue aging on the basis of studies of the age-related dynamics of cell structure, to establish the mutagenic effect of environmental factors on humans, etc.

In recent years, the cytogenetic method has gained great importance in connection with the possibilities of human genetic analysis, which were opened by the hybridization of somatic cells in culture. Obtaining interspecific hybrids of cells (for example, a human and a mouse) makes it possible to get much closer to solving problems associated with the impossibility of directed crosses, localize a gene on a certain chromosome, establish a linkage group for a number of characters, etc. Combining the genealogical method with the cytogenetic method, and also with the latest methods of genetic engineering has greatly accelerated the process of gene mapping in humans.

Biochemical methods for studying human heredity help to detect a number of metabolic diseases (carbohydrate, amino acid, lipid, etc.) using, for example, the study of biological fluids (blood, urine, amniotic fluid) by qualitative or quantitative analysis. The cause of these diseases is a change in the activity of certain enzymes.

With the help of biochemical methods, about 500 molecular diseases have been discovered, which are the result of the manifestation of mutant genes. With various types of diseases, it is possible either to determine the abnormal protein-enzyme itself, or to establish intermediate metabolic products. According to the results of biochemical analyzes, it is possible to diagnose the disease and determine the methods of treatment. Early diagnosis and the use of various diets at the first stages of postembryonic development can cure some diseases or at least alleviate the condition of patients with defective enzyme systems.

Like any other discipline, modern human genetics uses the methods of related sciences: physiology, molecular biology, genetic engineering, biological and mathematical modeling, etc. A significant place in solving the problems of medical genetics is occupied by the ontogenetic method, which allows us to consider the development of normal and pathological traits in the course of individual development.

Human hereditary diseases, their treatment and prevention. To date, more than 2,000 hereditary human diseases have been registered, and most of them are associated with mental disorders. 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.

Conditionally hereditary diseases can be divided into three large groups: metabolic diseases, molecular diseases, which are usually caused by gene mutations, and chromosomal diseases.

Gene mutations and metabolic disorders. Gene mutations can be expressed in an increase or decrease in the activity of certain enzymes, up to their absence. Phenotypically, such mutations manifest themselves as hereditary metabolic diseases, which are determined by the absence or excess of the product of the corresponding biochemical reaction.

Gene mutations are classified according to their phenotypic manifestation, i.e., as diseases associated with impaired amino acid, carbohydrate, lipid, mineral metabolism, and nucleic acid metabolism.

An example of a violation of amino acid metabolism is albinism, a relatively harmless disease that occurs in Western Europe with a frequency of 1:25,000. The cause of the disease is a defect in the tyrosinase enzyme, as a result of which the conversion of tyrosine to melanin is blocked. Albinos have milky skin, very fair hair, and no pigment in the iris. They have an increased sensitivity to sunlight, which causes inflammatory skin diseases in them.

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.

A number of pathological signs (hypertension, atherosclerosis, gout, etc.) are determined not by one, but by several genes (the phenomenon of polymerization). These are diseases with a hereditary predisposition, which are more dependent on environmental conditions: under favorable conditions, such diseases may not manifest themselves.

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 the Shereshevsky-Turner syndrome (44 + X), which manifests itself in women who are characterized by pathological changes in physique (short stature, short neck), disorders in the development of the reproductive system (absence of most female secondary sexual characteristics), mental limitation. The frequency of occurrence of this anomaly is 1:4000-5000.

Trisomic women (44+XXX), as a rule, are characterized by disorders 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's syndrome (44+XXY) are characterized by impaired 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, is the most studied. 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's 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).

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.

The main way to prevent hereditary diseases is their prevention. To this end, in many countries of the world, including Belarus, there is a network of institutions that provide medical genetic counseling to the population. 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 having a baby with severe hereditary ailments.

In the case of the birth of a sick child, sometimes its medication, dietary and hormonal treatment is possible. Poliomyelitis can serve as a clear example confirming the possibilities of medicine in the fight against hereditary diseases. This disease is characterized by hereditary predisposition, but the direct cause of the disease is a viral infection. Carrying out mass immunization against the causative agent of the disease made it possible to save all children who are hereditarily predisposed to it from the severe consequences of the disease. Dietary and hormonal treatment has been successfully used in the treatment of phenylketonuria, diabetes mellitus and other diseases.

Progress in the development of medicine and society leads to a relative increase in the share of genetically determined pathology in morbidity, mortality, and social disadaptation (disability).

More than 4000 nosological forms of hereditary diseases are known. About 5-5.5% of children are born with hereditary or congenital diseases.

Type and prevalence of hereditary pathology in children

With age, the “profile” of hereditary pathology changes, but the “burden” of the pathology does not decrease. Although the frequency of severe forms of hereditary diseases is reduced due to mortality in childhood, new diseases appear during puberty and later. After 20-30 years, diseases with a hereditary predisposition begin to appear.

Half of spontaneous abortions are due to genetic causes.

At least 30% of perinatal and neonatal mortality is due to congenital malformations and hereditary diseases with other manifestations. An analysis of the causes of child mortality in general also shows the significant importance of genetic factors.

The contribution of hereditary and congenital diseases to infant and child mortality in developed countries (according to WHO)

At least 25% of all hospital beds are occupied by patients suffering from diseases with a hereditary predisposition.

As you know, a significant proportion of social spending in developed countries goes to provide for disabled people from childhood. The role of genetic factors in the etiology and pathogenesis of disabling conditions in childhood is enormous.

The significant role of hereditary predisposition in the occurrence of widespread diseases (ischemic heart disease, essential hypertension, peptic ulcer of the stomach and duodenum, psoriasis, bronchial asthma, etc.) has been proven. Therefore, for the treatment and prevention of this group of diseases encountered in the practice of doctors of all specialties, it is necessary to know the mechanisms of interaction between environmental and hereditary factors in their occurrence and development.

Medical genetics helps to understand the interaction of biological and environmental factors (including specific ones) in human pathology.

A person is faced with new environmental factors that have never been encountered before throughout his evolution, he experiences great social and environmental loads (excess of information, stress, atmospheric pollution, etc.). At the same time, medical care is improving in developed countries, living standards are rising, which changes the direction and intensity of selection. A new environment can increase the level of the mutation process or change the expression of genes. Both will lead to an additional appearance of hereditary pathology.

Knowledge of the basics of medical genetics allows the doctor to understand the mechanisms of the individual course of the disease and choose the appropriate methods of treatment. On the basis of medical genetic knowledge, the skills of diagnosing hereditary diseases are acquired, as well as the ability to refer patients and their families to medical genetic counseling for primary and secondary prevention of hereditary pathology.

The acquisition of medical genetic knowledge contributes to the formation of clear guidelines in the perception of new medical and biological discoveries, which is necessary for the medical profession to the full, since the progress of science quickly and profoundly changes clinical practice.

Hereditary diseases for a long time did not respond to treatment, and the only method of prevention was the recommendation to refrain from childbearing. Those times are gone.

Modern medical genetics has armed clinicians with methods of early, presymptomatic (preclinical) and even prenatal diagnosis of hereditary diseases. Methods of pre-implantation (before embryo implantation) diagnostics are being intensively developed and are already being used in some centers.

Understanding the molecular mechanisms of the pathogenesis of hereditary diseases and high medical technologies have ensured the successful treatment of many forms of pathology.

A coherent system for the prevention of hereditary diseases has developed: medical genetic counseling, preconception prophylaxis, prenatal diagnosis, mass diagnosis of hereditary metabolic diseases in newborns that can be corrected by dietary and drug correction, clinical examination of patients and their families. The introduction of this system reduces the frequency of birth of children with congenital malformations and hereditary diseases by 60-70%. Doctors and public health organizers can actively participate in the implementation of the achievements of medical genetics.

The importance of genetics for medicine and health care

The subject and tasks of human genetics. Human genetics, or medical genetics, studies the phenomena of heredity and variability in various populations of people, the features of the manifestation and development of normal (physical, creative, intellectual abilities) and pathological signs, the dependence of diseases on genetic predetermination and environmental conditions, including social conditions. life. The formation of medical genetics began in the 1930s. XX century, when facts began to appear confirming that the inheritance of traits in humans obeys the same patterns as in other living organisms.

The task of medical genetics is to identify, study, prevent and treat hereditary diseases, as well as to develop ways to prevent the harmful effects of environmental factors on human heredity.

Methods for studying human heredity. When studying the heredity and variability of a person, the following methods are used: genealogical, twin, cytogenetic, biochemical, dermatoglyphic, hybridization of somatic cells, modeling, etc.

The genealogical method allows you to find out family ties and trace the inheritance of normal or pathological traits among close and distant relatives in this family on the basis of drawing up a pedigree - genealogy. If there are pedigrees, then, using summary data for several families, it is possible to determine the type of inheritance of a trait - dominant or recessive, sex-linked or autosomal, as well as its monogenicity or polygenicity. The genealogical method has proven the inheritance of many diseases, such as diabetes, schizophrenia, hemophilia, etc.

The genealogical method is used for the diagnosis of hereditary diseases and medical genetic counseling; it allows for genetic prophylaxis (prevention of the birth of a sick child) and early prevention of hereditary diseases.

The twin method consists in studying the development of traits in twins. It allows you to determine the role of the genotype in the inheritance of complex traits, as well as to evaluate the influence of such factors as upbringing, training, etc.

It is known that in humans, twins are identical (monozygous) and fraternal (dizygotic). Identical, or identical, twins develop from one egg fertilized by one sperm. They are always the same sex and strikingly similar to each other, as they have the same genotype. In addition, they have the same blood type, the same fingerprints and handwriting, even their parents confuse them and do not distinguish them by the smell of a dog. Only identical twins are 100% successful in organ transplants, since they have the same set of proteins and the transplanted tissues are not rejected. The proportion of identical twins in humans is about 35--38% of their total number.

Fraternal, or dizygotic, twins develop from two different eggs, simultaneously fertilized by different spermatozoa. Dizygotic twins can be of the same or different sexes, and from a genetic point of view, they are no more similar than ordinary brothers and sisters.

The study of identical twins throughout their lives, especially if they live in different socio-economic and natural-climatic conditions, is interesting because the differences between them in the development of physical and mental properties are explained not by different genotypes, but by the influence of environmental conditions.

The cytogenetic method is based on a microscopic examination of the structure of chromosomes in healthy and sick people. Cytogenetic control is used in the diagnosis of a number of hereditary diseases associated with aneuploidy and various chromosomal rearrangements. It also makes it possible to study tissue aging on the basis of studies of the age-related dynamics of cell structure, to establish the mutagenic effect of environmental factors on humans, etc.

In recent years, the cytogenetic method has gained great importance in connection with the possibilities of human genetic analysis, which were opened by the hybridization of somatic cells in culture. Obtaining interspecific hybrids of cells (for example, a human and a mouse) makes it possible to get much closer to solving problems associated with the impossibility of directed crosses, localize a gene on a certain chromosome, establish a linkage group for a number of characters, etc. Combining the genealogical method with the cytogenetic method, and also with the latest methods of genetic engineering has greatly accelerated the process of gene mapping in humans.

Biochemical methods for studying human heredity help to detect a number of metabolic diseases (carbohydrate, amino acid, lipid, etc.) using, for example, the study of biological fluids (blood, urine, amniotic fluid) by qualitative or quantitative analysis. The cause of these diseases is a change in the activity of certain enzymes.

With the help of biochemical methods, about 500 molecular diseases have been discovered, which are the result of the manifestation of mutant genes. With various types of diseases, it is possible either to determine the abnormal protein-enzyme itself, or to establish intermediate metabolic products. According to the results of biochemical analyzes, it is possible to diagnose the disease and determine the methods of treatment. Early diagnosis and the use of various diets at the first stages of postembryonic development can cure some diseases or at least alleviate the condition of patients with defective enzyme systems.

Like any other discipline, modern human genetics uses the methods of related sciences: physiology, molecular biology, genetic engineering, biological and mathematical modeling, etc. A significant place in solving the problems of medical genetics is occupied by the ontogenetic method, which allows us to consider the development of normal and pathological traits in the course of individual development.

Human hereditary diseases, their treatment and prevention. To date, more than 2,000 hereditary human diseases have been registered, and most of them are associated with mental disorders. 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.

Conditionally hereditary diseases can be divided into three large groups: metabolic diseases, molecular diseases, which are usually caused by gene mutations, and chromosomal diseases.

Gene mutations and metabolic disorders. Gene mutations can be expressed in an increase or decrease in the activity of certain enzymes, up to their absence. Phenotypically, such mutations manifest themselves as hereditary metabolic diseases, which are determined by the absence or excess of the product of the corresponding biochemical reaction.

Gene mutations are classified according to their phenotypic manifestation, i.e., as diseases associated with impaired amino acid, carbohydrate, lipid, mineral metabolism, and nucleic acid metabolism.

An example of a violation of amino acid metabolism is albinism, a relatively harmless disease that occurs in Western Europe with a frequency of 1:25,000. The cause of the disease is a defect in the tyrosinase enzyme, as a result of which the conversion of tyrosine to melanin is blocked. Albinos have milky skin, very fair hair, and no pigment in the iris. They have an increased sensitivity to sunlight, which causes inflammatory skin diseases in them.

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.

A number of pathological signs (hypertension, atherosclerosis, gout, etc.) are determined not by one, but by several genes (the phenomenon of polymerization). These are diseases with a hereditary predisposition, which are more dependent on environmental conditions: under favorable conditions, such diseases may not manifest themselves.

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 the Shereshevsky-Turner syndrome (44 + X), which manifests itself in women who are characterized by pathological changes in physique (short stature, short neck), disorders in the development of the reproductive system (absence of most female secondary sexual characteristics), mental limitation. The frequency of occurrence of this anomaly is 1:4000-5000.

Trisomic women (44+XXX), as a rule, are characterized by disorders 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's syndrome (44+XXY) are characterized by impaired 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, has been studied to the greatest extent. 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's 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).

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.

The main way to prevent hereditary diseases is their prevention. To this end, in many countries of the world, including Belarus, there is a network of institutions that provide medical genetic counseling to the population. 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 having a baby with severe hereditary ailments.

In the case of the birth of a sick child, sometimes its medication, dietary and hormonal treatment is possible. Poliomyelitis can serve as a clear example confirming the possibilities of medicine in the fight against hereditary diseases. This disease is characterized by hereditary predisposition, but the direct cause of the disease is a viral infection. Carrying out mass immunization against the causative agent of the disease made it possible to save all children who are hereditarily predisposed to it from the severe consequences of the disease. Dietary and hormonal treatment has been successfully used in the treatment of phenylketonuria, diabetes mellitus and other diseases.