genealogical method consists in the study of pedigrees based on Mendeleev's laws of inheritance and helps to establish the nature of the inheritance of a trait (dominant or recessive).

This is how inheritance is established individual characteristics human: facial features, height, blood type, mental and mental warehouse, 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.

The genealogical method is most often used in the genetics of mental illness. Its essence lies in tracing the manifestations of pathological signs in the pedigrees using the methods of clinical examination, indicating the type of family ties between family members.

This method is used to determine the type of inheritance of a disease or a particular trait, determine the location of genes on chromosomes, and assess the risk of mental pathology during medical genetic counseling. In the genealogical method, 2 stages can be distinguished - the stage of compiling pedigrees and the stage of using genealogical data for genetic analysis.

Drawing up a pedigree begins with the person who was examined first, he is called a proband. Usually this is a patient or an individual who has manifestations of the trait being studied (but this is not necessary). The pedigree should contain brief information about each family member, indicating his relationship to the proband. The pedigree is represented graphically using standard notation, as shown in Fig. 16. Generations are indicated in Roman numerals from top to bottom and placed to the left of the pedigree. Arabic numerals designate individuals of the same generation sequentially from left to right, while brothers and sisters or siblings, as they are called in genetics, are arranged in the order of their date of birth. All members of the pedigree of one generation are located strictly in one row and have their own code (for example, III-2).

According to the data on the manifestation of the disease or some property under study in the members of the pedigree, with the help of special methods of genetic and mathematical analysis, the problem of establishing the hereditary nature of the disease is solved. If it is established that the pathology under study is of a genetic nature, then at the next stage the problem of establishing the type of inheritance is solved. It should be noted that the type of inheritance is established not by one, but by a group of pedigrees. Detailed description pedigree is important for assessing the risk of manifestation of pathology in a particular member of a particular family, i.e. during medical genetic counseling.

When studying the differences between individuals on any basis, the question arises about the causal factors of such differences. Therefore, in the genetics of mental illness, the method of assessing the relative contribution of genetic and environmental factors to interindividual differences in susceptibility to a particular disease is widely used. This method is based on the assumption that the phenotypic (observable) value of a trait in each individual is the result of the influence of the individual's genotype and the environmental conditions in which it develops. However, it is almost impossible to determine this for a specific person. Therefore, appropriate generalized indicators are introduced for all people, which then allow, on average, to determine the ratio of genetic and environmental influences on an individual.

The study of the families of persons suffering from mental illness by the genealogical method has convincingly shown the accumulation of cases of psychoses and personality anomalies in them. An increase in the incidence of illness among close relatives was found for patients with schizophrenia, manic-depressive psychosis, epilepsy, and some forms of oligophrenia. The summary data are given in the table.

Risk of disease for relatives of the mentally ill (percentage)

In genetic analysis, it is important to take into account the clinical form of the disease. In particular, the frequency of schizophrenia among relatives largely depends on the clinical form of the disease that the proband suffers from. The table shows data reflecting this pattern:

The risk values ​​given in the tables allow the doctor to navigate in matters of inheritance of the disease. For example, the presence in the family (besides the proband itself) of another sick relative increases the risk for other family members, not only when both or one parent are sick, but also when other relatives are sick (siblings, aunts, uncles, etc.). ).

Thus, close relatives of patients with mental illness have an increased risk for a similar illness. In practice, it is possible to distinguish: a) high-risk groups - children, one of whose parents is ill with a mental illness, as well as siblings (brothers, sisters), dizygotic twins and parents of patients; b) the highest risk groups - children of two sick parents and monozygotic twins, one of whom fell ill. Early diagnosis, timely qualified psychiatric care are the essence of preventive measures in relation to this contingent.

The results of clinical genetic studies form the basis of medical genetic counseling in psychiatry. Medical genetic counseling can be schematically summarized in the following steps:

establishing the correct diagnosis of the proband;

compiling a genealogy and studying the mental state of relatives (for a correct diagnostic assessment, in this case, completeness of information about the mental state of family members is especially important);

determination of the risk for the disease based on the data;

assessment of the degree of risk in terms of "high - low". Risk data is communicated in a form appropriate to the needs, intentions and mental state consulting person. The doctor must not only report the degree of risk, but also help to correctly assess the information received, weighing all the pros and cons. Guilt should also be removed from the counselor for transmitting a predisposition to disease;

formation of an action plan. The doctor helps in choosing one or another decision (only spouses themselves can have children or refuse to have children);

catamnesis. Follow-up of the family seeking advice may provide the clinician with new information that helps to clarify the degree of risk.

The terms "gene pool" and "genogeography" belong to population genetics. As a science about the genetic processes occurring in the population of any kind of organisms and about the diversity of genes, genotypes and phenotypes of the population generated by these processes, population genetics dates back to 1908, with the formulation of the first genetic principle, now known as the Hardy-Weinberg genetic equilibrium principle. It is significant that the genetic processes that occur specifically in human populations, in particular, one of their specific manifestations - the stable preservation of the frequency of such a Mendelian trait as brachydactyly in many generations, served as an incentive to formulate the principle of genetic balance, which is of universal importance for populations of any species of bisexual organisms. .

This method is aimed at studying the inheritance of mental disorders in families of patients by comparing the frequency of the corresponding pathology in these families and among population groups living in similar natural and climatic conditions. Such groups of people in genetics are called a population. In this case, not only geographical, but also economic, social and other conditions of life are taken into account.

The genetic characteristics of populations makes it possible to establish their gene pool, factors and patterns that determine its preservation and change from generation to generation, which is achieved by studying the characteristics of the spread of mental illness in different populations, which, in addition, makes it possible to predict the prevalence of these diseases in subsequent generations.

The genetic characterization of a population begins with an estimate of the prevalence of the disease or trait under study in the population. These data are used to determine the frequencies of genes and corresponding genotypes in the population.

The first work done using this method was published in 1924. The results, from the point of view of the author, indicate that the intelligence of adopted children depends more on the social status of biological parents than on adopted ones. However, as noted by R. Plomin and co-authors, this work had a number of defects: only 35% of the 910 children examined were adopted under the age of 5 years; the measurement of mental abilities was carried out on a rather rough (only three-point) scale. The presence of such flaws complicates the meaningful analysis of the study.

The study of genealogy has been carried out by man since ancient times. In the 18-19 centuries, the analysis of human pathology (morbidity) began to be widely used. Thus, a genealogical line began to form. Subsequently, both the line of compiling pedigrees and the line of searching for options for statistical analysis of the available data were improved.

The clinical and genealogical method is a method of studying pedigrees, the use of which makes it possible to trace the distribution of pathology in a genus or family, indicating the type of relationship between their members.

This study option is considered universal. The genealogical method is widely used in solving problems of a theoretical nature. In particular, this research method is used for:

Establishing the nature of heredity in a trait;

Determining the type of inheritance of a disease or trait;

Evaluation of penetrance (frequency of manifestation) of the gene;

Analysis of the mapping process (determining the position of a gene relative to others on the chromosome) and linkage of genes;

Study of the intensity of the mutation process;

Deciphering the mechanisms on which the interaction of genes is based.

In modern medicine, a fairly large number of genetic pathologies are known. That is why a program has been developed to study every pregnant woman for six.

Phenylketonuria;

Androgenital syndrome;

Galactosemia;

Cystic fibrosis.

The genealogical method may be in some cases the only way, using which you can determine the type of inheritance of the disease in the family, find out the nature of the pathology, evaluate the prognosis of the disease, make a differentiated diagnosis with others prevention, treatment, adaptation and rehabilitation.

The genealogical method involves the compilation of a genealogy and its graphic representation.

In the course of these events, it is carried out about the proband (the individual studied by the specialist) and his family. As a rule, studies are carried out with a patient or a carrier of the trait under study. However, the genealogical method can be used not only in medicine.

In one parental couple, children are called sibs (brothers and sisters). If there is only one parent - half-sibs. They can be consanguineous (with a common father) or consanguineous (with a common mother).

As a rule, the compilation of a pedigree is carried out in order to study several (or one) diseases (signs). The amount of information may depend on the number of generations involved in it (pedigree).

An analysis of the information obtained involves taking into account a number of features when identifying the types of inheritance.

So, for example, the autosomal dominant type is indicated by the frequent detection of a trait in the pedigree (almost in every generation), in boys and girls equally often. The presence of a trait in one of the parents contributes to the appearance of it in half or all of the offspring.

When compiling pedigrees, each generation should be located on its own horizontal or radius. Generations are numbered in Roman numerals, and family members in Arabic numerals.

If there are several hereditary diseases in the family, unrelated to each other, for each pathology the pedigree is compiled separately.

Sections: Biology

Educational and research work of students (UIRS) at the Cheremkhovo Medical College during the period of professional training is one of the main forms of independent work of students

UIRS - is one of the active methods of teaching activity nature, which meets the new requirements of the Federal State Educational Standard. The student in the process of professional training independently has to a large number scientific - methodological and specialized literature to find individual theoretical calculations, as well as independently conduct instrumental and laboratory studies with subsequent analysis of the results.

During the UIRS, students form certain general cultural and professional competencies through the development of intellectual and professional skills (work with literature of a different nature, highlight the main thing, be able to analyze, plan their activities, make an assumption, conduct research, analyze results, draw conclusions, etc. e).

UIRS is a student's own creative work with final conclusions and judgments on the work, where students express their potential as a future researcher, showing interest in research work and understanding its necessity.

The presented work was carried out in accordance with the requirements for UIRS.

Purpose of the study

Practical significance: Training in the skills of compiling and analyzing a pedigree. Development of a memo on the compilation and analysis of pedigrees. Education of students on genealogy issues, development of interest in a deeper study of the problem.

Genealogical method as a universal method for studying human heredity

Kovalchuk Elena
2nd year student, specialty "Nursing"
Regional state budgetary educational institution
secondary vocational education
"Cheremkhovo Medical College"
scientific director - Sklyarova Svetlana Vladimirovna

Introduction

At present, according to World Organization About 10,000 hereditary diseases are known to health care, which are becoming increasingly important in the general pathology of a person. Harmful gene mutations are considered the main cause of hereditary diseases. Medical genetics is the study of human hereditary diseases. For the diagnosis of hereditary pathology in medical genetics, the genealogical method is used. This method is accessible and informative, it makes it possible to establish the heritable nature of the disease, the type of transmission of the defective gene, to trace possible risk its manifestations in close relatives.

The choice of the topic is due to the interest in studying the genealogy of my family, since in our family there are often recurring diseases, it became necessary to study its hereditary nature.

Purpose of the study: the use of the genealogical method in order to identify hereditary diseases in the genus.

Object of study: genealogy of the Kovalchuk family of Elena Igorevna on the mother's side.

Research objectives:

1. Analyze the scientific basis of the genealogical method.
2. way practical application method to draw up a family tree.
3. Make an analysis of the pedigree, identify the nature and type of inherited traits.
4. Develop a memo on the compilation and analysis of pedigrees.

Mresearch methods: study and analysis of general and special literature, observation, interview method, qualitative analysis of the pedigree.

Practical significance: Training in the skills of compiling and analyzing a pedigree. Development of a memo on the compilation and analysis of pedigrees. Education of students on questions of genealogy.

Chapter 1

Thus, the genealogical method is widely used in solving theoretical and applied problems: establishing the hereditary nature of a trait; determining the type of inheritance of the disease. Determine the prognosis of the disease and calculate the risk to the offspring.

In the genealogical method, 2 stages can be distinguished: Stage 1 - compilation of genealogies; Stage 2 - use of genealogical data for genetic analysis.

Chapter 2

Thus, drawing up a pedigree taking into account the basic rules and requirements will allow a successful qualitative analysis of the pedigree, which, in turn, will provide the most complete information about the nature and type of the inherited trait, as well as determine the likelihood of transferring the trait to subsequent generations.

Chapter 3 Criteria for Inheritance Types

Thus, having studied the criteria for the types and features of the inheritance of traits, it becomes possible to more accurately establish the nature of the inheritance of traits in the studied pedigree and suggest the likelihood of a gene manifestation in subsequent generations.

Chapter 4

4.1 Drawing up a pedigree

In order to identify the presence of inherited diseases in the genus, a pedigree was compiled, taking into account the basic requirements ( Application).

The “legend of the pedigree” was determined, which includes: a brief record with an accurate description of the family members and their relationship with the proband, information about the health status of the pedigree members, information about the nature of the inheritance of the disease and the features of its manifestation, about the onset and nature of the course of the disease, about age. The information was obtained by interviewing relatives, primarily parents, as well as grandparents. The collected information made it possible to analyze the pedigree, namely, to establish whether the trait is inherited, and also to understand the nature of the inheritance of this disease.

4.2 Pedigree analysis

In order to establish hereditary patterns, a genetic analysis of the pedigree was carried out, which showed:

In the first, third and fourth generations, one case of tonsillitis is noted in the vertical direction - this indicates the hereditary nature of the trait, since these are recurring cases of the disease. Tonsillitis is not a hereditary disease, therefore, a hereditary predisposition to this disease is determined, which is based on a decrease in the immune response to the causative agent of the disease.

An autosomal dominant type of inheritance of the trait has been established, since in the first, third and fourth generations there is one case of tonsillitis in women, that is, there is a direct transmission of the trait from one of the sick parents to children, in this case from mother to child (daughters) - this is typical for this type of trait inheritance.

This type of inheritance confirms the fact that the disease did not manifest itself in the second generation, this indicates incomplete penetrance of the descendants of a sick person, that is, a person, being outwardly healthy, but he passes on to his children the genes responsible for this disease, or a predisposition to it, as in our case.

This type of inheritance is characterized by an increase in the severity of pathological disorders in subsequent generations, which can be corrected through preventive measures.

Thus, the results of the analysis of the pedigree made it possible to establish:

1. The nature of the inherited trait is a hereditary predisposition to a decrease in the immune response to the causative agent of tonsillitis;
2. Determine the type of inherited trait as autosomal dominant.
3. Assume that subsequent generations from the proband can inherit this trait.
4. To avoid the increase in the severity of pathological disorders in subsequent generations, it is necessary to carry out preventive measures.

Conclusion

This study was aimed at applying the genealogical method in order to identify hereditary diseases in the genus.

Special literature on this issue has been studied, the content of which reflects the scientific basis of the genealogical method. A theoretical study of the issue indicates the relevance of studying human genetics in connection with the increased manifestation of hereditary diseases, including the timely diagnosis of hereditary diseases.

An important role in the diagnosis of this category of diseases is assigned to the genealogical method. This method is characterized by high efficiency, as it is the most informative, and also accessible to any person interested in the history of the development of his family or clan, including the presence of hereditary diseases in the family.

In the process of applying the genealogical method in practice, a pedigree was compiled and its qualitative analysis was made. The results of the analysis showed:

1. The presence in the genus of a hereditary predisposition to tonsillitis, which is based on a decrease in the immune response to the pathogen.
2. The predisposition to the disease is transmitted along the female vertical line.
3. Inheritance of the trait refers to the autosomal dominant type of inheritance.
4. With this type of trait inheritance, an increase in the severity of pathological disorders in subsequent generations is characteristic.

Thus, the analysis of the pedigree allows us to understand its hereditary nature, that is, it was possible to establish the nature and type of the inherited trait.

The genealogical method confirms its universality, as it made it possible to determine the nature and type of inheritance of a trait, to suggest a risk for future generations. Remains the most accessible and informative method in diagnostics genetic diseases.

In the course of the work, according to the results of the study, it was found that the manifestation of genetic diseases, as well as a decrease in the increase in the severity of pathological disorders in subsequent generations, can be avoided by implementing preventive measures.

Compliance with the recommended preventive measures that ensure the maintenance of a healthy lifestyle will prevent frequent exacerbations of the disease, reduce the risk of developing an increase in the severity of pathological disorders in subsequent generations and, accordingly, reduce the likelihood of the proband passing the mutant gene to subsequent generations.

In this way, healthy lifestyle of life is the key to preventing the manifestation of not only non-hereditary, but also genetic diseases in humans.

genealogical method

a method of studying the nature of the inheritance of a particular trait or assessing the likelihood of its occurrence in the future among members of the family under study, based on finding out family ties (pedigree) and tracing the trait among all relatives.

1. Small medical encyclopedia. - M.: Medical Encyclopedia. 1991-96 2. First health care. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic dictionary of medical terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what the "Genealogical method" is in other dictionaries:

A method for studying the nature of inheritance of a particular trait or assessing the likelihood of its occurrence in the future among members of the family under study, based on finding out family ties (pedigree) and tracing the trait among all relatives ... Big Medical Dictionary

GENEALOGICAL METHOD- [cm. genealogy] a method of studying the nature of the inheritance of a particular trait or assessing the likelihood of its occurrence in the future among members of the family under study; G. m. is used in the study of the nature of the inheritance of traits (for example, diseases) ... Psychomotor: Dictionary Reference

genealogical method- in human genetics, the method of analyzing pedigrees. It is used to study the nature of the distribution of hereditary traits in families. It is more often used in medicine for the genetic analysis of various pathological abnormalities ... Dictionary of Psychogenetics

genealogical method- refers to psychogenetic methods. A study of the similarities between relatives in different generations is being carried out. This requires accurate knowledge of a number of characteristics of direct relatives on the maternal and paternal lines and coverage as much as possible ... ...

psychogenetic method- (method of psi "genetics) methods that make it possible to determine the influence of hereditary factors and the environment on the formation of certain mental characteristics of a person (see psychogenetics). These include: 1) the twin method is the most informative; 2) method ... ... Great Psychological Encyclopedia

psychogenetics- (from the Greek genetikos, referring to birth, origin) an area of ​​​​psychology bordering on genetics. The subject of P. is the origin of individual psychological features human, elucidation of the role of the genotype and environment in their formation. P … Great Psychological Encyclopedia

Psychogenetics (Greek psyche soul and Greek genesis origin) is the science of heredity and variability of mental and psychophysiological properties, which arose at the intersection of psychology and genetics. In Western Literature ... Wikipedia

A branch of psychology that uses genetic data and the genealogical method. The subject of psychogenetics is the interaction of heredity and environment in the formation of interindividual variability of human psychological properties (cognitive and ... ... Psychological Dictionary

A section of human genetics devoted to the study of the role of hereditary factors in human pathology at all major levels of life organization from population to molecular genetic. The main section of M.g. constitutes clinical genetics, ... ... Medical Encyclopedia

A branch of genetics closely related to anthropology and medicine. G. hours are conditionally divided into anthropogenetics, which studies heredity and variability normal signs of the human body, and medical genetics (See Genetics ... ... Great Soviet Encyclopedia

I Heredity is the property inherent in all organisms to ensure, in a number of generations, the continuity of signs and features of development, i.e., the morphological, physiological and biochemical organization of living beings and the nature of their individual ... ... Medical Encyclopedia

A person as an object of genetic research has almost no advantages over other objects.

On the contrary, there are many obstacles that make it difficult to study its genetics: 1) the impossibility of arbitrary crossing in the experiment; 2) late onset of puberty; 3) a small number of descendants in each family; 4) the inability to equalize living conditions for offspring; 5) the lack of accurate registration of the manifestation of hereditary properties in families and the absence of homozygous lines; 6) a large number of chromosomes; 7) and the most important difficulty in studying human genetics in a capitalist society is social inequality, which makes it difficult to realize a person's hereditary potentials.

Despite these difficulties, genetics has developed some methods that allow you to study heredity and inheritance in humans step by step. There are several research methods: genealogical, cytogenetic, twin, ontogenetic and population.

It should be borne in mind that any trait, regardless of whether it is a wild type trait, i.e., refers to the norm, or is associated with any disease, can serve as a model for the study of heredity. Protecting a person from hereditary diseases or damage to his heredity is as important as finding out the inheritance of the norm. At present, genetic methods have been developed mainly in relation to morphological traits that are genetically determined quite clearly (brachydactyly, albinism, color blindness, spotting of the skin and hair, etc.).

The genetic study of mental properties still remains problematic, since elementary criteria for a trait in the genetic sense have not been found for them. Almost all signs of a person’s mental and creative activity are so complex and complex, and are also largely determined by external, including social, factors that it is still difficult to carry out a genetic analysis of these properties, although their hereditary conditionality is beyond doubt.

It can be said that the great majority of the traits that characterize the species Homo sapiens can be studied as quantitative and complex physiological traits, i.e., traits that do not show a discrete character in ontogeny. These traits are controlled by the genotype system (polygenic). And until this system is unraveled, at least on the example of simply organized organisms, the problem of signs of behavior remains inaccessible for genetic analysis. On the contrary, mutant traits that go beyond the characteristics of species traits serve as good genetic models for studying heredity and inheritance in the norm.

Discrete mutant traits cannot be viewed as only pathological traits, allegedly having no adaptive value. It is possible that the very appearance of a person with developed hemispheres of the cerebral cortex, a vertical position of the body, and discrete speech signaling is the result of major mutations. This is strongly supported by

a short period of time in human evolution, during which small mutations could hardly accumulate in such a quantity and give such a significant evolutionary effect. A reasonable person is as “unusual” for nature as a domestic chicken that lays 365 eggs a year instead of 10-15, or a record-breaking cow that gives 16 thousand kg of milk a year instead of 600-700 kg.

The division of traits into normal and mutant in relation to humans and animals is necessary for the knowledge of human evolution and pathological phenomena.

The totality of species characteristics of humans and animals is determined by the genotype system, which has developed under the influence of all selection factors in the process of evolution. Mutations that are heterozygous in humans seem to be just as necessary as in animals to maintain them in the population.

The most dangerous thing in the development of scientific methods for the study of animals and man, especially his abilities, is the anthropomorphic moment, that is, wishful thinking.

genealogical method

An analysis of human inheritance based on the compilation of a pedigree - genealogy was proposed by F. Galton.

genealogical method is a study of the inheritance of human properties according to pedigrees (pedigry). This method is applicable if 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 and there is a sufficient number of descendants in each generation, or in the case when there are data on a sufficient number different families allowing to identify similarities in pedigrees. Data on a set of similar pedigrees is subjected to statistical processing.

The most widely used system for designating human pedigrees was proposed by G. Yust in 1931.

On the basis of a large number of analyzed families, pedigrees are compiled and mathematical calculations are made according to the type of inheritance of a particular trait - dominant or recessive, often and not often occurring mutations, sex-linked or not, etc. Here we will not touch on the application of the mathematical method to this analysis, we only note that this entire formal analysis is based on elementary genetic patterns of inheritance.

Pedigree inheritance patterns of a dominant autosomal gene that determines a trait, such as a disease (chondrodystrophic dwarfism, bullous epidermolysis - the ability of the skin to form large blisters with minor injuries, retinoblastoma, etc.), or a morphological defect, such as short fingers (brachydactyly - the absence of two distal phalanges in fingers).

The inheritance of traits determined by recessive genes (recessive inheritance) is analyzed somewhat more complicated when drawing up pedigree charts.

For example, two in a family, the appearance of two sick children is equal to the product of probabilities, i.e. 0.25 X 0.25, i.e. 6.25%.

Frequently occurring recessive autosomal genes, provided that their carriers (aa) are able to marry and produce offspring, will be in high concentration in the population. In this case, marriages aa X Aa become very likely, in the offspring from which the inheritance of this trait will imitate inheritance according to the dominant type 1: 1. However, knowing the type of inheritance and manifestation of those and other genes, even in the case of small families, but with a sufficient number of such families, it is possible to establish the true nature of inheritance.

The inheritance of genes that are fully sex-linked, i.e., located in non-homologous segments, and partially sex-linked - localized in homologous segments of X- and Y-chromosomes, obeys the patterns established for sex chromosomes. For dominant and recessive genes, this inheritance will be defined differently depending on where the gene is located - in the homologous or non-homologous segment of the X and Y chromosomes, and how it is transmitted. So, the dominant gene that causes webbed fingers, located in the non-homologous segment of the Y chromosome, is inherited from fathers and manifests itself only in men.

For partially floor-linked dominant genes located in the homologous segments of the sex chromosomes, the analysis is somewhat more difficult, but also possible. An example of sex-linked inheritance of a recessive trait is the inheritance of hemophilia. There is a discontinuity in the transmission of this trait in generations; affected males are descendants of healthy mothers who were heterozygous for the gene; women with hemophilia can be descendants of a sick father and a sick or healthy mother.

About 50 sex-linked recessive genes have been found in humans. Interestingly, about half of them cause eye disease. It has long been known that the degree of transmission of hereditary traits in related (inbreeding) and unrelated marriages (outbreeding) is different. Once genetics has established patterns of more frequent manifestation of recessive genes during inbreeding, there is no need to argue at length about the harm of consanguineous marriages. The higher the inbreeding coefficient, the more likely the occurrence of hereditary diseases in generations. AT different countries among different peoples and classes of society, as well as in different eras, family marriages (between cousins, second cousins ​​and sisters) occur with different frequencies. So, for example, in villages on the Fiji Islands, the number of related marriages reaches 29.7%, in some castes of India - 12.9, in Japan (Nagasaki) - 5.03, in Holland - 0.13-0.159, in Portugal - 1 40, in the USA (Baltimore) - 0.05%, etc. The percentage of consanguineous marriages varies in different regions of the same country, depending on the way of life.

The harmfulness of consanguineous marriages is hardly noticeable in individual pedigrees, but with a comparative statistical analysis of diseases and mortality, it appears with complete obviousness.

A striking example of the detection of a recessive gene in consanguineous marriage.

In this pedigree, kinship is maintained through the marriage of siblings (brothers and sisters) of varying degrees of kinship. From two consanguineous marriages (fourth cousin siblings) 4 out of 8 children appeared in one family, and 2 out of 5 in the other, suffering from hereditary amaurotic idiocy. K. Stern suggests that one of the two common ancestors of these lines passed this recessive gene through three generations to each of the four parents.

Sometimes the disease and mortality of children from related marriages exceed by 20-30% those from unrelated marriages. It is obvious that the reason for the phenomenon under consideration is genetic, namely: a high probability of the manifestation of hereditary diseases and mortality as a result of homozygotization of recessive genes that determine physiological deficiencies and mortality (lethal and semi-lethal genes).

So, the genealogical method is a very valuable method, but its importance in research is the greater, the more accurate and deeper the pedigrees are compiled. With the growth of civilization and more accurate registration of pedigrees, the role of this method in human genetics will increase.

twin method

twins called the offspring, consisting of simultaneously born individuals in singletons (humans, horses, cattle, sheep, etc.).

Twins can be identical or fraternal.

identical, or identical, twins(OB) develop from one egg fertilized by one spermatozoon, when two or more embryos arise from a zygote instead of one embryo (polyembryony). Due to the fact that the mitotic division of the zygote gives two equally hereditary blastomeres, identical twins, no matter how many they develop, must be hereditarily identical and of the same sex. This phenomenon is an example of asexual, or rather, vegetative reproduction of animals.

fraternal twins(RB) develop from simultaneously ovulated different eggs, fertilized by different spermatozoa. And since different eggs and sperm cells can carry different combinations of genes, fraternal twins can be hereditarily as different as children of the same married couple born in different time. Fraternal twins can be of the same (RBR) or different sex (RBR).

More often in the literature, instead of the term "fraternal twins" (RB), the term "fraternal twins" (DB) is used, since twins are more common. However, the term "fraternal twins" better emphasizes the difference between OB and RB; identical twins are also more likely to be born as twins.

Judging by the data obtained on mammals, there can be several hypotheses to explain the formation of OB in humans:

• divergence of blastomeres during the first division of the zygote and separate development of the embryo from these blastomeres;
• separation of a group of cells at the blastocyst stage (before gastrulation);
• separation of embryos at an early stage of gastrulation. The most likely way is the second one.

The number of twins in one birth in a person varies: twins are most common, triplets are less common, quadruples are even rarer, and five are very rare. According to I. I. Kanaev, over the past 150 years, four cases of quintuplets have been found in the United States, and two cases in Canada. The fact of the birth of OB - five girls who survived to adulthood - is known in the family of the Canadian farmer Dionne (1934). It is calculated that quintuplets are born once in 54,700,816 births, gears - in 4,712 million births, septuplets are known only as an exception. On average, the birth rate of twins is 1% with fluctuations in the range of 0.5-1.5%. Twins are less viable, and therefore their number at birth is less than at conception, and in adulthood less than at birth.

The calculation of the frequency of OB in relation to RB is based on the theoretical ratio of same-sex and opposite-sex couples of RB at the birth of twins: 25%♀♀ + 50%♀♂ + 25%♂♂ female) will give a difference in the number of OB pairs, which on average ranges from 21 to 33.4% of all twins.

For the use of twins in genetic studies, it is very important to accurately diagnose the type of AB and the type of RP. Diagnosis is made on the basis of the following criteria:

1. OBs must be of the same sex, RBs can be of the same sex or different sexes;
2. OB have, as a rule, one common chorion, RB - different chorions;
3. reciprocal tissue transplantation in OB is as successful as autotransplantation, it is impossible in RB;
4. the presence of similarity (concordance) in OB and dissimilarity (discordance) in RB in many ways.

For diagnosis, one should choose signs that are clearly inherited and are least susceptible to change under the influence of environmental factors; such signs include blood groups, pigmentation of the eyes, skin and hair, skin relief (fingerprints, palms, feet, etc.). If one or two of these features reveal a difference between twins, then they are, as a rule, RB.

All dubious cases of twin diagnosis can be caused either by a developmental disorder of one of the OB partners, or by the similarity of the parents in a number of ways. However, the latter is extremely rare. It should be noted that the developmental disorder of one of the OB partners is usually explained by the unequal action of factors intrauterine life and the occurrence of somatic mutations in the early stages of embryonic development, before the formation of organs. Various gene and chromosomal rearrangements, monosomy and other mutations that occur in one of the partners can cause significant differences in the OB phenotype. Therefore, it is necessary to take into account the possibility of somatic mutations in OB in early embryogenesis.

According to the generalizations of I. I. Kanaev, outlined in his excellent monograph, the essence of the twin method in genetics is reduced to the following provisions:

1) the OB pair has an identical combination, the RB pair has different combinations of the genotypes of the parents;

2) for both partners of one pair of OBs, the external environment may turn out to be the same, and for the other - different. If OB partners experience different influences throughout their lives, this will lead to an intra-pair difference. Hence, pairs can be with intra-pair identical and intra-pair different environments.

Comparison of OBs with the same environment with OBs with a different environment opens up the possibility of judging the role of the influence of the environment on intra-pair differences in twins throughout life. Comparison of OB with the same environment and RB with the same environment allows you to find out the role of the hereditary factor. This kind of study is carried out on a large sample and processed statistically.

Based on the difference in the genetic origin of OB and RB, it follows that if there are no differences in OB for the same traits and there are such in RB, then it is obvious that these differences in traits in the latter are due to hereditary factors. If, however, intra-pair differences in the same traits occur in one and the other type of twins, then it is obvious that they can be caused by environmental factors. From the data of discordance in OB and RB for a number of morphological features, it can be seen that the intra-pair difference in RB occurs many times more often than in OB.

Some data of S. Reed on the comparative frequency of pathology in the second partner in the case of illness of one of the twins are presented.

The percentage shows the frequency of disease concordance in two types of twins, it shows that if one partner fell ill with one of the indicated diseases, then the probability of the second disease in OB is much higher than in RB. VP Efroimson, analyzing the data on the frequency of contordant pairs, absolutely correctly points out that a high hereditary predisposition of OB to diseases manifests itself in the presence of a provoking factor; without it, this percentage will be much lower.

The twin method makes it possible to determine with the greatest accuracy the hereditary predisposition of a person to a number of diseases and properties. By other methods it is very difficult or almost impossible to study many infectious and tumor diseases, inflammations of the skin and various organs, as well as the characteristics of normal human nervous activity.

When using the twin method, it is necessary to take into account the conditions of joint and separate education in the lives of partners, social conditions in which they are located, etc. Nevertheless, the twin method allows you to most accurately determine the coefficient of heritability of different traits, as well as to judge the heterogeneity of the population according to the studied genes and isolate the role of the environment in determining the variability of the studied traits.

Cytogenetic method

Cytogenetic method in human genetics, a cytological analysis of a person's karyotype in normal and pathological conditions is usually called.

It is more correct to call this method cytological rather than cytogenetic, since genetic analysis by crossing in humans is excluded, and carriers of chromosomal disorders, if they survive, are usually infertile. However, occasionally, in relation to some chromosomal disorders, it is possible to combine the cytological method with the genealogical one and to establish a connection between the phenotypic effect and a certain type of chromosomal changes. Due to these circumstances, it is possible to retain the term “cytogenetic method” accepted in the literature in the study of human genetics. In those cases where such parallelism is not being studied, the use of this term is not authorized.

The cytogenetic method is used to investigate various kinds of heteroploidy and chromosomal rearrangements in human somatic tissues, which cause various phenotypic deviations from the norm.

Most often, this method is used in tissue culture. It allows to take into account large chromosome anomalies that occur both in germ and somatic cells. It turned out that in humans, as well as in animals, trisomics and monosomics quite often arise for different pairs of chromosomes due to non-disjunction of autosomes and sex chromosomes during meiosis. Trisomy and monosomy for sex chromosomes in humans are detected based on the analysis of sex chromatin.

In the course of a relatively long individual development of a person, chromosome anomalies (chromosomal rearrangements, as well as a change in the number of chromosomes) accumulate in the cells of various tissues. Body tissues are diverse populations of genetically different cells, in which the concentration of cells with pathological nuclei increases with age. In this case, the cytogenetic method makes it possible to study tissue aging based on the study of cell structures in the age dynamics of the "population" of somatic and generative tissues.

Since the frequency of occurrence of chromosomal abnormalities depends on the influence of various mutagens on the body (ionization, chemical agents - pharmacological preparations, the gas composition of the environment, etc.), the cytogenetic method makes it possible to establish the mutagenic effect of environmental factors on a person.

The use of the cytogenetic method has especially expanded in connection with the discovery of the causes of a number of physical and mental diseases - the so-called chromosomal diseases.

There are several human diseases, for example, Klinefelter's disease, Shereshevsky-Turner's disease, Down's disease, and others, the causes of which remained unknown for a long time until chromosomal abnormalities were detected in such patients by cytological methods.

Sick men with Klinefelter's syndrome are characterized by underdevelopment of the gonads, degeneration of the seminiferous tubules, mental retardation, disproportionate growth of the limbs, etc. Shereshevsky-Turner syndrome occurs in women. It manifests itself in delayed puberty, underdevelopment of the gonads, absence of menstruation, infertility, short stature, and other pathological signs.

It turned out that both of these syndromes in offspring are the result of nondisjunction of sex chromosomes during the formation of parental gametes. Due to the non-disjunction of the X chromosomes in the female homogametic) sex, during meiosis, gametes can occur with two X chromosomes, i.e. XX + 22 autosomes, and without X chromosomes, i.e. 0 + 22; in the male (heterogametic) sex, respectively, the gametes XY + 22 and 0 + 22. In the case of fertilization of such eggs by normal spermatozoa (X + 22 or Y + 22), the following classes of zygotes can be formed: XXX + 44, 0X + 44 and XXY + 44, 0Y+44.

It follows from this that the number of chromosomes in zygotes of different origin can vary from 47 to 45, and individuals 0Y + 44, obviously, do not survive, since they have never been found. The chromosome set XXY + 44 is inherent in a man with Klinefelter's syndrome (male intersexuality), the chromosome sets X0 + 44 and XXX + 44 are found in women with Shereshevsky-Turner syndrome.

Upon further analysis of patients with different syndromes, it turned out that due to nondisjunction of sex chromosomes, different type chromosomal abnormalities, in particular polysomy. There are, for example, men with such sets of chromosomes: XX Y, XXX Y, XXXX Y, and women - XXX, XXXX.

The peculiarity of the role of sex chromosomes in the determination of sex in humans in the case of their non-disjunction, in contrast to Drosophila, was manifested in the fact that the XX Y chromosome set always determines the male sex, and the X0 set determines the female sex. At the same time, an increase in the number of X chromosomes in combination with one Y chromosome does not change the definition of male, but only enhances Klinefelter's syndrome. Trisomy, or polysomy on the X chromosome, in women also often causes diseases similar to Shereshevsky-Turner syndrome.

Diseases caused by a violation of the normal number of sex chromosomes are diagnosed by a cytological method - analysis of sex chromatin. In those cases when the tissues of men have a normal set of sex chromosomes - XY, sex chromatin is not found in the cells. In normal women - XX - it is found in the form of a single body. With X chromosome polysomy in women and men, the number of sex chromatin bodies is always one less than the number of X chromosomes, i.e. n x \u003d n X - 1. So, in the cells of men with Klinefelter syndrome, when XX Y is recruited, there is one body sex chromatin, with a set of XXXY - two, with a set of XXXXY - three; in women with Shereshevsky-Turner syndrome, respectively: X0 - no body, XXX - two bodies, XXXX - three sex chromatin bodies, etc. It is assumed that only one of the X chromosomes is genetically active in each such zygote. The rest of the chromosomes go into a heteropyknotic state in the form of sex chromatin.

The reasons for this pattern have not been elucidated, but it is assumed that it is associated with the leveling of the action of sex chromosome genes in the hetero- and homogametic sex.

As we know, nondisjunction of chromosomes can occur not only in meiosis, but also in somatic cells during the entire embryogenesis of an animal, starting from the first cleavages of the egg. Due to the latter, among people with a violation of the divergence of the sex chromosomes, sick female mosaics and male mosaics may appear. For example, mosaics of the following types are described: double: X0/XX, X0/XXX and X0/XY, X0/XYY, triple: X0/XX/XXX, XX/X0/XY, as well as quadruple mosaics, when somatic cells of one humans contain four different sets of chromosomes.

In addition to the considered type of diseases caused by a change in the number of sex chromosomes in the zygote, chromosomal diseases can be caused by nondisjunction of autosomes and various kinds of chromosomal rearrangements (translocations, deletions). So, for example, in children with congenital idiocy - Down's disease, accompanied by short stature, wide round face, closely spaced by narrow palpebral fissures and a half-open mouth, trisomy on chromosome 21 was detected. It has been established that the incidence of Down's disease in newborns depends on the age of mothers.

A wide variety of diseases are associated with congenital chromosomal abnormalities. Therefore, the cytogenetic method is of great importance in the etiology of human diseases.

population method

population method allows you to study the distribution of individual genes or chromosomal abnormalities in human populations.

The population method is based on mathematical methods. To analyze the genetic structure of a population, it is necessary to examine a large sample, which must be representative - objectively reflect the entire general population, i.e., the entire population as a whole. In the examined sample, the distribution of persons is established according to the corresponding clearly defined phenotypic classes, the differences between which are hereditarily determined. Then, based on the found phenotypic frequencies, gene frequencies are determined.

Based on the knowledge of gene frequencies, it is possible to describe the analyzed population in accordance with the Hardy-Weinberg formula and predict in advance the likely nature of splitting in the offspring of individuals belonging to one or another phenotypic class. The study of gene frequencies is important for assessing the consequences of consanguineous marriages, as well as for elucidating the genetic history of the human population as a whole.

The frequency of distribution in populations of different anomalies turns out to be different; while the vast majority of the corresponding recessive alleles are presented in the heterozygous state.

So, approximately every hundredth inhabitant of Europe is heterozygous for the gene of amaurotic idiocy (Spielmeier-Vogt disease), while they get sick with this disease in adolescence out of 1 million, only 25 people are homozygous. Albinos in European countries occur with a frequency of 1 in 20,000, although the heterozygous state of this allele is inherent in every seventieth inhabitant.

The situation is somewhat different in the case of anomalies that are inherited sex-linked, an example of which is color blindness - color blindness, which is controlled, apparently, by a number of alleles distributed over two closely linked loci on the X chromosome. Among the male population, the frequency of color blindness (q) corresponds to the total frequency of recessive alleles and was, for example, in Moscow in the 30s, according to R. I. Serebrovskaya, 7%, while at the same time, among the female population of the same population, color blindness was only 0.5% (q 2), but in the heterozygous state, approximately 13% of women carry alleles that cause color blindness.

As we said above, considering the genealogical method, the probability of the appearance of recessive homozygotes in the offspring may be different when persons with different degrees of kinship marry. So, for spouses who are in relation to each other cousins and sisters, the probability of having children homozygous for the recessive allele, common in the population with a frequency q, will no longer be q 2, but a large value, namely q / 16 (1 + 15q).

This is due to the fact that if one of the common ancestors of such spouses - a grandmother or grandfather - carried a recessive allele in the heterozygote, then with a probability of 1/16 this allele will be transmitted to both cousins.

The harmful effects of consanguineous marriages are particularly evident in isolated populations of limited size, the so-called isolates. An isolate is a group of individuals of a population that mostly marry individuals of their group and therefore are characterized by a significant coefficient of consanguinity. Such isolates can be separate isolated villages, communities, etc. Within an isolate, related marriages (inbreeding) are more likely, and spouses are more likely to carry the same mutant genes, which results in an increase in the likelihood of manifestation of recessive alleles in the homozygous state. Different isolates carry different concentrations of similar or different genes.

In the Marianas and the island of Guam, the mortality among the local population from amyotrophic lateral sclerosis (associated with damage to the cells of the anterior horns of the spinal cord) is more than 100 times higher than the mortality from this disease in other countries. In southern Panama, in the province of San Blas, a very prominent part of the Carib Kuna tribe are albinos, who appear here in every generation. In one village on the river. Rhone in Switzerland, among 2,200 inhabitants, there are more than 50 deaf-mutes, and 200 more have some hearing impairments. In all likelihood, in all such cases of a sharp increase in the concentration of individual alleles, a certain role is played by genetic drift, uneven reproduction in the past of individual families, genera, and a decrease in migration.

As civilization grows and the productive forces of society develop, the number of isolates decreases, and their importance for the population as a whole decreases. However, they still exist.

Knowledge of gene frequencies, as already mentioned, makes it possible to predict the nature of splitting in the offspring of individual phenotypic classes of parental individuals.

Based on the Hardy-Weinberg formula, it can be shown that with monogenic inheritance, splitting by phenotype in the offspring of dominant mothers should be carried out in the ratio p (1 + pq) of dominants to p recessives, or (l + pq): q 2; in the offspring of recessive mothers, the phenotype split should be pq 2: q 3 , or p: q.

Let's take an example. In one study, when studying the Rh factor, the frequency of the recessive rh allele in the population was 0.4, and the frequency of the dominant allele of Rh was 0.6. Hence, it was to be expected that in the offspring of Rh-positive mothers, the frequency of Rh-positive children (Rh +) would be approximately 7.8 times higher than the frequency of Rh-negative children (Rh -); in the offspring of Rh-negative mothers, the corresponding excess will be 1.5 times.

The actual ratios in the surveyed sample were:

• in the first case 1475 Rh + : 182 Rh - , or 8.1: 1,
• in the second case 204 Rh + : 129 Rh - , or 1.6: 1.

Thus, the observed splitting results are in very good agreement with the theoretically expected results predicted from gene frequency analysis.

Population analysis of polymorphism by blood groups is interesting in that it helps to understand the dynamics of the genetic structure of different populations and helps to identify relationships between them.

Different populations differ significantly in their genetic structure, in particular in blood types. At the same time, it is possible to trace some quite clear patterns. If the concentration of the I B allele is highest in the region of India and China, then to the east and west of this region it gradually drops down to zero among the indigenous inhabitants of America and Australia. At the same time, in the American Indians (and the natives of Australia and Polynesia), the concentration of the allele I 0 reaches a maximum. Allele I A is rare in the indigenous population of America, as well as in India, Arabia, tropical Africa, and Western Europe.

To explain these differences in the genetic structure of populations, a hypothesis has recently been proposed, according to which the decisive factor in the selection in relation to the blood groups of the AB0 system was plague and smallpox epidemics. The causative agent of the plague, Pasteuvella pestis, having the property of antigen 0, is most detrimental to people with blood type 0, since such individuals are not able to produce enough antibodies in the event of an infection. For a similar reason, the smallpox virus is most dangerous for people with blood group A. Where the plague raged (India, Mongolia, China, Egypt), there was an intensive elimination of the I 0 allele, and where smallpox was especially rampant (America, India, Arabia, tropical Africa), the allele 1 A was eliminated first of all. In areas of Asia, where plague and smallpox were endemic, the allele 1 c received the highest frequency.

In Chapter 5, we reviewed the monogenic inheritance of sickle cell anemia due to splitting of the S alleles. the result is a system of balanced hereditary polymorphism.

Thus, in both examples of the analysis of polymorphism by blood groups and sickle cell anemia, we see how the use of the population method allows us to reveal the genetic structure of human populations.

ontogenetic method

ontogenetic method allows you to establish the carriage of recessive alleles in the heterozygous state and chromosomal rearrangements by phenotype.

The genetic basis for the manifestation of recessive genes in the heterozygous state is, apparently, an incomplete block in the synthesis chain of one or another metabolite caused by the action of the dominant allele of this gene.

It is known that some hereditary diseases manifest themselves not only in persons homozygous for the alleles that cause the disease, but in an erased form in heterozygotes as well. Therefore, methods for determining heterozygous carriage in ontogeny are currently being intensively developed. So, a heterozygous carrier of phenylketonuria (an increased content of phenylalanine in the blood is determined by the additional administration of phenylalanine and subsequent determination of its (or tyrosine) level in the blood plasma. The presence of heterozygosity for this allele is established by an increased content of phenylalanine. alleles) the level of phenylalanine does not change. Normally, the catalase enzyme necessary for carbohydrate metabolism is present in the blood, but there is a gene that causes the absence of catalase in the homozygous state. catalase activity without much overlap between dominant and recessive homozygotes.

Catalase activity can accurately identify heterozygous and homozygous carriers of the acatalase allele among close relatives and parents.

Heterozygous carriage of the allele that determines Duchenne muscular dystrophy is tested by the activity of creatine phosphokinase. Now similar tests have been developed for 40 hereditary diseases determined by recessive alleles.

At present, the ontogenetic method has been enriched by biochemical, immunological, and molecular methods of research, which are described in a number of special manuals.

The importance of the ontogenetic method is obvious for establishing the carrier state of a recessive gene in a heterozygous state in relatives of a family in which a hereditarily ill child appears. Diagnostics in ontogeny is important for calculating the probability of the appearance of hereditarily ill offspring in related and mixed marriages. As heterozygous carrier testing becomes easier, this method will need to be introduced to counsel couples about the possibility of their children developing the disease, as well as to study the spread of mutations in populations.

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