The genealogical method is its significance. Methods for studying human genetics

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. In the process of professional training, a student independently has to find separate theoretical calculations from a large number of scientific, methodological and specialized literature, as well as independently conduct instrumental and laboratory research followed by analysis of the results obtained.

When conducting 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 of 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 adviser - 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, and to trace the possible risk of its manifestation 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. It remains the most accessible and informative method in the diagnosis of 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.

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

The basis of this method is the compilation and analysis of pedigrees. This method is widely used from ancient times to the present day in horse breeding, selection of valuable lines of cattle and pigs, in obtaining purebred dogs, as well as in breeding new breeds of fur animals. Human genealogies have been compiled over many centuries in relation to the reigning families in Europe and Asia.

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

When compiling pedigrees, the source is a person - a proband, whose pedigree is being studied. Usually this is either a patient, or a carrier of a certain trait, the inheritance of which needs to be studied. When compiling genealogical tables, the symbols proposed by G. Yust in 1931 are used (Fig. 6.24). Generations are denoted by Roman numerals, individuals in a given generation are designated by Arabic numerals.

Rice. 6.24. Conventions when compiling pedigrees (according to G. Just)

With the help of the genealogical method, the hereditary conditionality of the trait under study can be established, as well as the type of its inheritance (autosomal dominant, autosomal recessive, X-linked dominant or recessive, Y-linked). When analyzing pedigrees for several traits, the linked nature of their inheritance can be revealed, which is used when compiling chromosome maps. This method allows one to study the intensity of the mutation process, to evaluate the expressivity and penetrance of the allele. It is widely used in medical genetic counseling to predict offspring. However, it should be noted that genealogical analysis becomes much more complicated when families have few children.

Pedigrees in autosomal dominant inheritance. The autosomal type of inheritance is generally characterized by an equal probability of occurrence of this trait in both men and women. This is due to the same double dose of genes located in the autosomes of all representatives of the species and received from both parents, and the dependence of the developing trait on the nature of the interaction of allelic genes.

When a trait dominates in the offspring of a parental pair, where at least one parent is its carrier, it manifests itself with a greater or lesser probability, depending on the genetic constitution of the parents (Fig. 6.25).

Rice. 6.25. The probability of the appearance of offspring with a dominant trait from different married couples (/- III)

If a trait is analyzed that does not affect the viability of the organism, then the carriers of the dominant trait can be both homo- and heterozygotes. In the case of dominant inheritance of some pathological trait (disease), homozygotes, as a rule, are not viable, and carriers of this trait are heterozygotes.

Thus, with autosomal dominant inheritance, the trait can occur equally in men and women and can be traced with a sufficient number of offspring in each generation along the vertical. Analyzing pedigrees, it is necessary to remember the possibility of incomplete penetration of the dominant allele, due to the interaction of genes or environmental factors. The penetrance index can be calculated as the ratio of the actual number of carriers of a trait to the number of expected carriers of that trait in a given family. It must also be remembered that some diseases do not appear immediately from the moment the child is born. Many diseases inherited according to the dominant type develop only at a certain age. So, Huntington's chorea is clinically manifested by the age of 35-40, polycystic kidney disease also manifests itself late. Therefore, when predicting such diseases, brothers and sisters who have not reached a critical age are not taken into account.

The first description of a pedigree with an autosomal dominant type of inheritance of an anomaly in humans was given in 1905. It traces the transmission in a number of generations brachydactyly(short-fingered). On fig. 6.26 shows a pedigree with this anomaly. On fig. 6.27 shows a pedigree with retinoblastoma in a case of incomplete penetrance.

Pedigrees in autosomal recessive inheritance. Recessive traits appear phenotypically only in homozygotes for recessive alleles. These traits, as a rule, are found in the offspring of phenotypically normal parents - carriers of recessive alleles. The probability of occurrence of recessive offspring in this case is 25%. If one of the parents has a recessive trait, then the probability of its manifestation in the offspring will depend on the genotype of the other parent. In recessive parents, all offspring will inherit the corresponding recessive trait (Fig. 6.28).

Rice. 6.26. Pedigree ( A) with an autosomal dominant type of inheritance (brachydactyly - B)

For pedigrees with an autosomal recessive type of inheritance, it is characteristic that the trait does not appear in every generation. Most often, recessive offspring appear in parents with a dominant trait, and the likelihood of such offspring appears in closely related marriages, where both parents can be carriers of the same recessive allele obtained from a common ancestor. An example of autosomal recessive inheritance is the pedigree of a family with pseudohypertrophic progressive myopathy, in which closely related marriages are frequent (Fig. 6.29). Draws attention to the spread of the disease in the last generation horizontally.

Rice. 6.27. Pedigree with retinoblastoma in case of incomplete penetrance

Rice. 6.28. Probability of having offspring with a recessive trait

from various married couples ( I-IV)

Pedigrees with dominant X-linked inheritance of a trait. Genes located on the X chromosome and having no alleles on the Y chromosome are present in the genotypes of men and women in different doses. A woman receives her two X chromosomes and the corresponding genes from both her father and mother, while a man inherits his only X chromosome from his mother. The development of the corresponding trait in men is determined by the single allele present in its genotype, while in women it is the result of the interaction of two allelic genes. In this regard, traits inherited according to the X-linked type are found in the population with different probability in males and females.

With dominant X-linked inheritance, the trait is more common in women due to their greater ability to receive the corresponding allele from either their father or mother. Men can only inherit this trait from their mother. Women with a dominant trait pass it on equally to their daughters and sons, while men only pass it on to their daughters. Sons never inherit a dominant X-linked trait from their fathers.

Rice. 6.29. Pedigree with autosomal recessive inheritance (pseudohypertrophic progressive myopathy)

An example of this type of inheritance is the pedigree described in 1925 with follicular keratosis - skin disease, accompanied by loss of eyelashes, eyebrows, hair on the head (Fig. 6.30). Characteristic is a more severe course of the disease in hemizygous men than in women, who are most often heterozygotes.

In some diseases, the death of male hemizygotes in the early stages of ontogenesis is observed. Then in the pedigrees among the affected should be only women, in whose offspring the ratio of affected daughters, healthy daughters and healthy sons is 1:1:1. Male dominant hemizygotes that do not die at very early stages of development are found in spontaneous abortions or among the stillborn. Such features of inheritance in humans are characterized by pigmentary dermatosis.

Pedigrees with recessive X-linked inheritance of traits. A characteristic feature of pedigrees with this type of inheritance is the predominant manifestation of the trait in hemizygous men who inherit it from mothers with a dominant phenotype, who are carriers of the recessive allele. As a rule, the trait is inherited by men through the generation from maternal grandfather to grandson. In women, it manifests itself only in the homozygous state, the likelihood of which increases with closely related marriages.

The most famous example of recessive X-linked inheritance is hemophilia. The inheritance of hemophilia type A is presented in the pedigree of the descendants of the English Queen Victoria (Fig. 6.31).

Rice. 6.30. Pedigree with an X-linked dominant type of inheritance (follicular keratosis)

Rice. 6.31. Pedigree with X-linked recessive inheritance (hemophilia type A)

Another example of inheritance by this type is color blindness - a certain form of color vision disorder.

Pedigrees in Y-linked inheritance. The presence of the Y-chromosome only in males explains the peculiarities of the Y-linked, or hollandric, inheritance of the trait, which is found only in men and is transmitted through the male line from generation to generation from father to son.

Rice. 6.32. Pedigree with Y-linked (Holandric) type of inheritance

One trait whose Y-linked inheritance in humans is still debated is ear hypertrichosis, or the presence of hair on the outer edge of the ear. It is assumed that in addition to this gene, the short arm of the Y chromosome contains genes that determine the male sex. In 1955, a Y-linked transplantation antigen, called HY, was described in the mouse. Perhaps it is one of the factors of sexual differentiation of male gonads, the cells of which have receptors that bind this antigen. The receptor-bound antigen activates male-type development of the gonad (see Sections 3.6.5.2; 6.1.2). This antigen has remained almost unchanged in the course of evolution and is found in the body of many animal species, including humans. Thus, the inheritance of the ability to develop gonads according to the male type is determined by the hollandic gene located on the Y chromosome (Fig. 6.32).

twin method

This method consists in studying the patterns of inheritance of traits in pairs of identical and dizygotic twins. It was proposed in 1875 by Galton initially to assess the role of heredity and environment in the development of a person's mental properties. At present, this method is widely used in the study of heredity and variability in humans to determine the relative role of heredity and environment in the formation of various signs, both normal and pathological. It allows you to identify the hereditary nature of the trait, determine the penetrance of the allele, evaluate the effectiveness of the action on the body of some external factors ( medicines, training, education).

The essence of the method is to compare the manifestation of a feature in different groups twins based on similarities or differences in their genotypes. monozygotic twins, developing from one fertilized egg are genetically identical, as they have 100% of common genes. Therefore, among monozygotic twins there is a high percentage concordant pairs, in which the trait develops in both twins. Comparison of monozygotic twins reared in different conditions postembryonic period, allows you to identify signs in the formation of which an essential role belongs to environmental factors. According to these signs, between the twins there is discordance, those. differences. On the contrary, the preservation of similarity between twins, despite the differences in the conditions of their existence, indicates the hereditary conditionality of the trait.

Comparison of paired concordance for this trait in genetically identical monozygotic and dizygotic twins, which have an average of about 50% of common genes, makes it possible to more objectively judge the role of the genotype in the formation of the trait. High concordance in pairs of monozygotic twins and significantly lower concordance in pairs of dizygotic twins indicate the importance of hereditary differences in these pairs for determining the trait. The similarity of the concordance index in mono- and dizygotic twins indicates an insignificant role of genetic differences and the determining role of the environment in the formation of a sign or the development of a disease. Significantly different, but rather low rates of concordance in both groups of twins make it possible to judge the hereditary predisposition to the formation of a trait that develops under the influence of environmental factors.

Establishment of the correlative role of heredity and environment in the development of various pathological conditions allows the doctor to correctly assess the situation and carry out preventive measures in case of hereditary predisposition to the disease or to carry out auxiliary therapy in case of hereditary conditionality.

The difficulties of the twin method are associated, firstly, with the relatively low birth rate of twins in the population (1:86-1:88), which complicates the selection of a sufficient number of pairs with this trait; secondly, with the identification of monozygosity of twins, which is of great importance for obtaining reliable conclusions.

A number of methods are used to identify monozygosity of twins. 1. A polysymptomatic method for comparing twins according to many morphological features (pigmentation of the eyes, hair, skin, hair shape and features of the hairline on the head and body, the shape of the ears, nose, lips, nails, body, finger patterns). 2. Methods based on the immunological identity of twins for erythrocyte antigens (ABO, MN, Rhesus systems), for serum proteins (γ-globulin). 3. The most reliable criterion for monozygosity is provided by a transplantation test using cross-grafting of the skin of twins.

Despite the laboriousness of the twin method and the possibility of errors in determining the monozygosity of twins, the high objectivity of the findings makes it one of the widely used methods of genetic research in humans.

The basic patterns of heredity established for living organisms are universal and fully valid for humans. However, as an object of genetic research, a person has its advantages and disadvantages.

It is impossible for humans to plan artificial marriages. Back in 1923, N.K. Koltsov noted that "... we cannot experiment, we cannot force Nezhdanova to marry Chaliapin just to see what kind of children they will have." However, this difficulty can be overcome thanks to the targeted selection of a large number of marriage pairs of those that correspond to the goals of this genetic study.

A large number of chromosomes - 2n = 4b - greatly complicates the possibilities of human genetic analysis. However, the development of new methods of working with DNA, the method of hybridization of somatic cells and some other methods eliminate this difficulty.

Due to the small number of descendants (in the second half of the 20th century, 2-3 children were born in most families), it is impossible to analyze splitting in the offspring of one family. However, in large populations, families with traits of interest to the researcher can be selected. In addition, in some families, certain signs have been traced over many generations. In such cases, genetic analysis is possible. Another difficulty is related to the duration of generational change in humans. One generation in humans takes an average of 30 years. And, therefore, a geneticist cannot observe more than one or two generations.

A person is characterized by a large genotypic and phenotypic polymorphism. The manifestation of many signs and diseases is highly dependent on the conditions external environment. It should be noted that the concept of "environment" for humans is broader than for plants and animals. Along with nutrition, climate, and other abiotic and biotic factors, human environment is also social factors that are difficult to change at the request of the researcher. At the same time, a person as a genetic object is widely studied by doctors of all specialties, which often helps to establish various hereditary abnormalities.

Currently, interest and attention to the study of human genetics is actively increasing. Yes, global international program The "Human Genome" aims to study the human genome at the molecular level. To solve it, all the latest modern methods of genetics and medicine are used.

What methods does human genetics have today? There are many of them: genealogical, twin, cytogenetic, population-statistical, biochemical, somatic cell genetics and molecular genetics. Let's take a closer look at each of them.

Being one of the main ones in human genetics, this method is based on genealogy - the doctrine of genealogies. Its essence is the compilation of a pedigree and its subsequent analysis. This approach was first proposed by the English scientist F. Galton in 1865.

genealogical method is widely used to solve both scientific and applied problems. It allows you to identify the hereditary nature of the trait and determine the type of inheritance. Along with this, the method makes it possible to establish linked inheritance, determine the type of gene interaction and allele penetrance. The genealogical method underlies medical genetic counseling. It includes two stages: compilation of pedigrees and their genealogical analysis.

Drawing up a pedigree. The collection of information about the family begins with a person called a proband. This is usually the patient with the disease being studied. Children of one parental couple are called sibs (brothers and sisters). In most cases, a pedigree is collected on one or more grounds. Pedigree can be full or limited. The more generations traced in the pedigree, the more complete it is and the higher the chances of obtaining completely reliable information. The collection of genetic information is carried out by questioning, questioning, personal examination of the family. The survey usually begins with relatives on the maternal side: maternal grandparents, indicating the grandchildren, children of each child of the grandparents. The pedigree includes information about miscarriages, abortions, stillborns, infertile marriages, etc.

When compiling a pedigree, a brief record of data on each member of the genus is kept, indicating its relationship in relation to the proband. Usually, the following are indicated: surname, name and patronymic, date of birth and death, age, nationality, place of residence of the family, profession, the presence of chronic diseases in the family, the cause of death of the deceased, etc.

After collecting information, they make a graphic representation of the pedigree using a system of symbols (Fig. 2.1).

In doing this, it is important to follow following rules:

1. Drawing up a pedigree begins with the proband. Siblings are listed in birth order from left to right, starting with the eldest.

2. All members of the pedigree are arranged strictly by generations in one row.

3. Generations are indicated by Roman numerals to the left of the pedigree from top to bottom.

4. Arabic numerals number the offspring of one generation (one row) from left to right.

5. Due to the fact that some diseases manifest themselves at different periods of life, the age of family members is indicated.

6. Personally examined members of the pedigree are noted.

The graphic representation of the pedigree can be vertical-horizontal or arranged in a circle (in the case of extensive data). The pedigree scheme is accompanied by a description of the designations under the figure, which is called a legend (Fig. 2.2).

Genetic analysis of the pedigree

The task of genetic analysis is to establish the hereditary nature of the disease and the type of inheritance, to identify heterozygous carriers of the mutant gene, as well as to predict the birth of sick children in families with hereditary pathology.

Pedigree analysis includes the following steps: 1. Establishing whether a given trait or disease is single in the family or there are several cases (family character). If a trait occurs several times in different generations, then it can be assumed that this trait has a hereditary nature. 2. Determining the type of trait inheritance. To do this, analyze the pedigree, taking into account the following points:

1) whether the studied trait is found in all generations and how many members of the pedigree have it;

2) whether its frequency is the same in both sexes and in which sex it occurs more often;

3) to persons of what sex the trait is transmitted from a sick father and a sick mother;

4) whether there are families in the pedigree in which sick children were born to both healthy parents, or healthy children were born to both sick parents;

5) what part of the offspring has an inherited trait in families where one of the parents is sick.

Autosomal dominant inheritance is characterized by the fact that the mutant gene is associated with an autosome and manifests itself in both homozygous (AL) and heterozygous (Aa) states. Because of this, the following features of inheritance can be traced:

1) transmission of pathology from sick parents to children;

2) both sexes are affected in equal proportions;

3) healthy family members usually have healthy offspring;

4) father and mother equally pass the mutant gene to daughters and sons. The disease can be passed from father to son.

The clinical manifestations of the disease can vary significantly depending on the expressivity and penetrance of the gene. Expressivity is the degree of gene expression (in our case, the severity of the disease). With a high expression of the gene, a severe, often fatal form of the disease develops, with a low expression, the person is outwardly healthy. Penetrance refers to the frequency of manifestation of a mutant gene among its carriers. It is determined by the ratio of the number of individuals with a given disease (or trait) to the number of individuals with a given gene, expressed as a percentage. For example, the penetrance of atherosclerosis is 40%, Marfan's syndrome is 30%, retinoblastoma is 80%, etc.

Depending on the type of inheritance, the overall picture of the pedigree looks different.

With an autosomal recessive type of inheritance, the mutated gene manifests its effect only in the homozygous state. For this reason, in the heterozygous state, it can exist for many generations without manifesting itself phenotypically.

With this type of inheritance, the disease is rare in the pedigree and not in all generations. The probability of the disease in girls and boys is the same. The trait can manifest itself in children whose parents were healthy, but were heterozygous carriers of the mutant gene. There are several options for such marriages:

1) mother aa x father aa - such parents will have all children sick (aa);

2) mother Aa x father aa - 50% of the children will be sick (genotype aa) and 50% phenotypically healthy (genotype Aa), but will be heterozygous carriers of the defective gene;

3) mother Aa x father Aa - 25% of children will be sick (genotype aa), 75% phenotypically healthy (genotypes AA and Aa), but 50% of them will be carriers of the mutant gene (genotype Aa).

Expressivity and penetrance vary widely (from 0 to 100%) and strongly depend on environmental conditions. According to the autosomal dominant type, polydactyly (six-fingered), brachydactyly (short-fingered), achondroplasia (dwarfism), Marfan's syndrome ("spider fingers") and other diseases are inherited (Fig. 2.3).

With a dominant type of inheritance, if one of the parents is sick (Aa), the probability of having a sick child is 50%, provided that the gene is completely penetrant. In the case of heterozygosity of both parents (Aa x Aa), sick children can be born with a probability of 75%. Many autosomal dominant diseases in the homozygous state are more severe than in heterozygotes. However, in practice it is not uncommon for carriers of a dominant gene to remain phenotypically healthy. As a result, the type of pedigree changes and gaps in generations appear.

Carrying a dominant gene without a phenotypic manifestation can be suspected in one of the parents if patients with the same dominant pathology appear among his descendants. When healthy parents have a sick child and there are other cases of this disease in the pedigree, it is legitimate to assume that one of the parents of the patient had a defective gene that did not penetrate, but was passed on to the descendant.

The dominant gene may have varying degrees of expressivity, which makes it difficult to establish an autosomal dominant mode of inheritance. Consider this on the example of a hereditary pathology of the connective tissue - Marfan's syndrome.

It is known that the incidence of hereditary recessive autosomal diseases is directly dependent on the prevalence of the mutant gene among the population. The frequency of such diseases is especially increased in isolates and among populations with a high percentage of consanguineous marriages. Such marriages have a negative effect on offspring, which is indicated by the fact that mental retardation among children from related marriages is 4 times higher than in families with unrelated marriages.

With an autosomal recessive type of inheritance (as with an autosomal dominant one), various degrees of expressiveness and penetrance of the trait are possible. Diseases with an autosomal recessive type of inheritance include many metabolic diseases, including phenylketonuria, galactosemia, albinism (Fig. 2.4), cystic fibrosis, etc. It has been established that recessive diseases are more often diagnosed at an early age.

The inheritance of sex-linked diseases is determined by the fact that the mutant gene is located on the X or Y chromosome. It is known that women have two X-sex chromosomes, and men have one X- and one Y-chromosome. In humans, more than 200 genes are located on the X chromosome. Genes located on the X chromosome can be recessive or dominant.

In women, the mutant gene may be on both X chromosomes or only one of them; in the first case it is homozygous, in the second it is heterozygous. Men, being hemizygous (have only one X chromosome), pass it only to daughters and never to sons. Any gene, both dominant and recessive, localized on its X chromosome will definitely show up. In that main feature X-linked inheritance.

X-linked recessive inheritance is characterized by the following features:

1) the disease is more common in males;

2) sick children can be born from healthy parents (if the mother is heterozygous for the mutant gene);

3) sick men do not transmit the disease to their sons, but their daughters become heterozygous carriers of the disease;

4) sick women can be born only in families where the father is sick and the mother is heterozygous for the mutant gene.

Let us consider several examples when a recessive gene is localized on the X chromosome. If a healthy woman and a sick man marry, then in such a family all children will be healthy, and daughters will receive one X chromosome with a mutant gene from their father and will be heterozygous carriers (because they will receive a second normal X chromosome from their mother) . In the event that a healthy man and a woman with a pathological gene enter into marriage, then the probability of having a sick boy will be 50% of all boys and 25% of all children.

The probability of the birth of sick girls is very low and is possible only if the father is sick and the mother is heterozygous for the mutant gene. In such a family, half of the boys will be sick. Among girls, half will show the disease, and the other half will carry the defective gene.

A classic example of recessive, sex-linked inheritance is hemophilia. Patients suffer from increased bleeding. The reason is the insufficient content of blood clotting factors in the blood. On fig. 2.5 shows the pedigree of a family with hemophilia

Pedigree analysis shows that only boys are affected. (II - 1.4; III - 7.15). This suggests that the hemophilia gene is sex-linked. Sick children are more often born from healthy parents and, therefore, the disease gene is recessive.

It is known that hemophilia is widespread in the royal families of Europe. This is due to the conclusion of closely related marriages. As a result, the resulting mutations persisted within the family. Queen Victoria of England was a carrier of the hemophilia gene. Her son Leopold was born a hemophiliac. Through her daughters and grandchildren, Queen Victoria passed on the hemophilia gene to Voldemar and Henry of Prussia, Friedrich of Hesse, Tsarevich Alexei Romanov, Ruprecht of Tech-Athlon, two Battenberg and two Spanish princes (Figure 2.6). In addition to hemophilia, recessive genes are localized on the X chromosome, causing Duchenne myopathy, some forms of color blindness, and other diseases.

When the dominant gene is localized on the X chromosome, the type of inheritance is called X-linked dominant. It is characterized by the following features:

1) both men and women are sick, but there are twice as many sick women as sick men;

2) the disease can be traced in every generation;

3) if a father is sick, then all his daughters will be sick, and all sons will be healthy;

4) if the mother is sick, then the probability of having a sick child is 50%, regardless of gender;

5) children will be sick only if one of the parents is sick;

6) healthy parents will have all children healthy.

According to the X-linked dominant type, phosphatemia (lack of phosphate in the blood), brown color of tooth enamel, etc. are inherited.

It has its own characteristics and Y-linked inheritance.

Few genes are located on the Y chromosome in males. They are only passed on to sons and never to daughters (Holandric inheritance). With the Y chromosome in men, traits such as hypertrichosis (presence of hair along the edge of the ears), skin membranes between the toes, development of the testes, growth rate of the body, limbs and teeth are inherited. Characteristic features of inheritance with the Y-chromosome can be seen in Fig. 2.7.

Modern clinical medicine can no longer do without genetic methods. To study hereditary traits in humans, various biochemical, morphological, immunological, and electrophysiological methods are used. Thanks to the progress of genetic technologies, laboratory genetic diagnostic methods can be performed on a small amount of material that can be sent by mail (a few drops of blood on filter paper, or even on one cell taken at an early stage of development (N. P. Bochkov, 1999) (Fig. 1.118).

Rice. 1.118. M. P. Bochkov (born in 1931)

In solving genetic problems, the following methods are used: genealogical, twins, cytogenetic, somatic cell hybridization, molecular genetic, biochemical, dermatoglyphics and palmoscopy methods, population statistical, genome sequencing, etc.

Genealogical method for studying human heredity

The main method of genetic analysis in humans is to compile and study the pedigree.

Genealogy is genealogy. Genealogical method - a method of pedigrees, when a trait (disease) is traced in the family, indicating family ties between members of the pedigree. It is based on a thorough examination of family members, compilation and analysis of pedigrees.

This is the most universal method for studying human heredity. It is always used when a hereditary pathology is suspected, it allows you to establish in most patients:

The hereditary nature of the trait;

Type of inheritance and allele penetrance;

The nature of the linkage of genes and carry out the mapping of chromosomes;

The intensity of the mutation process;

Deciphering the mechanisms of gene interaction.

This method used in genetic counseling.

The essence of the genealogical method is to establish family ties, symptoms or disease among close and distant, direct and indirect relatives.

It consists of two stages: drawing up a pedigree and genealogical analysis. The study of the inheritance of a trait or disease in a particular family begins with the subject who has that trait or disease.

The individual that first comes to the attention of a geneticist is called a proband. It is predominantly a patient or a carrier of exploratory signs. Children of one parental couple are called sibs of the proband (brothers - sisters). Then they go to his parents, then to the brothers and sisters of the parents and their children, then to the grandparents, etc. When compiling a pedigree, make short notes about everyone from family members, his family ties with the proband. The pedigree scheme (Fig. 1.119) is accompanied by symbols under the figure and is called a legend.

Rice. 1.119. Pedigree of the family where cataract is inherited:

patients with this disease are family members I - 1, I And - 4, III - 4,

The use of the genealogical method made it possible to establish the nature of the inheritance of hemophilia, brachydactyly, achondroplasia, etc. It is widely used to clarify the genetic nature of the pathological condition and to predict the health of offspring.

Methods of compiling pedigrees, analysis. Drawing up a pedigree begins with a proband - a personwho turned to a geneticist or a doctor and contains a trait that needs to be studied in relatives on the paternal and maternal lines.

When compiling genealogical tables, they use the conventions proposed by G. Yust in 1931 (Fig. 1.120). Pedigree figures are placed horizontally (or along circle), one line every generation. On the left, each generation is designated in Roman numerals, and individuals in a generation are designated in Arabic from left to right and from top to bottom. Moreover, the oldest generation is placed on top of the pedigree and is indicated by the number i, and the smallest is at the bottom of the pedigree.

Rice. 1.120. Symbols that are used in the compilation of pedigrees.

Brothers and sisters in connection with the birth of the eldest are located on the left. Each member of the pedigree has its own code, for example, II - 4, II And - 7. The marriage couple of the pedigree is indicated by the same number, but with a small letter. If one of the spouses is not married, the information O it is not given at all. All individuals are placed strictly by generations. If the pedigree is great, then different generations are arranged not in horizontal rows, but in concentric ones.

After drawing up the pedigree, a written explanation is attached to it - the legend of the pedigree. The following information is reflected in the legend:

Results of clinical and post-clinical examination of the proband;

Information about the personal search of relatives proband;

Comparison of the results of the personal examination of the proband according to the survey of his relatives;

Written information about relatives living in another area;

Conclusion regarding the type of disease inheritance or traits.

When compiling a pedigree, one should not be limited only to a survey of relatives - this is not enough. Some of them prescribe a complete clinical, post-clinical or special genetic examination.

The purpose of genealogical analysis is to establish genetic patterns. Unlike other methods, a genealogical survey must be completed by a genetic analysis of its results. Analysis of the pedigree makes it possible to draw a conclusion regarding the nature of the trait (hereditary or not), title, inheritance (autosomal dominant, autosomal recessive or sex-linked), zygosity of the proband (homo - or heterozygous), degree of penetrance and expressivity of the gene under study

Features of pedigrees with different types of inheritance: autosomal dominant, autosomal recessive and article-linked. An analysis of pedigrees shows that all diseases determined by the mutant gene obey the classical laws Mendel for different types inheritance.

According to the autosomal dominant type of inheritance, dominant genes are phenotypically manifested in the heterozygous state and therefore their identification and the nature of inheritance does not cause difficulties.

1) one of the parents is sick in each affected person;

2) in an affected person who is married to a healthy woman, on average, half of the children are sick, and the other half are healthy;

3) healthy children of the affected parent have healthy children and grandchildren;

4) men and women are affected equally often;

5) the disease must manifest itself in every generation;

6) heterozygous individuals affected.

An example of an autosomal dominant type of inheritance may be the nature of the inheritance of six-fingered (large-fingered). Six-fingered limbs are a rather rare phenomenon, but are persistently preserved in many generations of some families (Fig. 1.121). Bagatopalia is consistently repeated in the offspring if at least one of the parents is bugatopalia, and is absent in those cases when the limbs are normal in both parents. In the offspring of rich-toed parents, this trait is present in equal numbers in boys and girls. The action of this gene in ontogenesis appears quite early and has a high penetrance.

Rice. 1.121. Genus with an autosomal dominant type of inheritance.

With autosomal dominant inheritance, the risk of developing the disease in offspring, regardless of gender, is 50%, but the manifestations of the disease to a certain extent depend on penetrance.

Analysis of pedigrees shows that syndactyly, Marfan's disease, achondroplasia, brachydactyly, Osler's hemorrhagic telangiectasia, hemachromatosis, hyperbilirubinemia, hyperlipoproteinemia, various dysostoses, marble disease, incomplete osteogenesis, Recklinghausen's neurofibromatosis, otosclerosis, Peltzius-Merzbacher's disease, are inherited for this type. pelgirivska anomaly leukocytes, periodic adynamia, pernicious anemia, polydactyly, acute intermittent porphyria, hereditary ptosis, idiopathic thrombocytopenic purpura, thalassemia, tuberous sclerosis, favism, Charcot-Marie disease, Sturge-Weber disease, multiple exostoses, lens ectopia, elliptocytosis (L. O . Badalyan et al., 1971).

According to autosomal recessive inheritance, recessive genes phenotypically appear only in the homozygous state, which makes it difficult to both identify and study the nature of inheritance.

This type of inheritance is characterized by the following patterns:

1) if a sick child was born to phenotypically normal parents, then the parents are necessarily heterozygotes;

2) if the affected sibs were born from a closely related marriage, then this is evidence of the recessive inheritance of the disease;

3) if they marry a sick recessive disease and a genotypically normal person, all their children will be heterozygotes and phenotypically healthy;

4) if the marriage is ill and heterozygote, then half of their children will be affected, and half - heterozygous;

5) if two patients get married for the same recessive disease, then all their children will be sick.

6) men and women get sick with the same frequency:

7) heterozygotes are phenotypically normal, but are carriers of one copy of the mutant gene;

8) affected individuals are homozygous, and their parents are heterozygous carriers.

An analysis of pedigrees shows that the phenotype of the detection of recessive genes occurs only in those families where these genes have both parents at least in a heterozygous state (Fig. 1.122). Recessive genes in human populations remain undetected.

Rice. 1.122. Genus with an autosomal recessive type of inheritance.

However, in marriages between close relatives or in isolates (small groups of people), where marriages occur by close family ties, the expression of recessive genes increases. Under such conditions, the probability of a transition to a homozygous state and the phenotypic manifestation of rare recessive genes increases sharply.

Since most recessive genes have a negative biological significance and cause a decrease in vitality and the appearance of various virility and hereditary diseases, related marriages have a sharply negative character for the health of offspring.

Hereditary diseases are predominantly transmitted in an autosomal recessive manner, children from heterozygous parents can inherit diseases in 25% of cases (with complete penetrance). Given that complete penetrance is rare, the percentage of inheritance of the disease is also less.

According to the autosomal recessive type, the following are inherited: agammaglobulipemia, agranulocytosis, alkaptonuria, albinism (Fig. 1.123), amavrotic idiocy, aminoaciduria, autoimmune hemolytic anemia, hypochromic microcytic anemia, anencephaly, galactosemia, ger maphroditism (Fig. 1.124), hepagocerebral dystrophy, Gaucher disease, eunuchoidism , myxedema, sickle cell anemia, fructosuria, color blindness(L. O. Badalyan et al., 1971).

Rice. 1.123. - Inheritance by autosomal recessive type. Albinism.

Rice. 1.124. Autosomal recessive inheritance. Hermaphroditism.

A number of diseases are inherited according to the X-chromosomal (sex-linked) type, when the mother is a carrier of the mutant gene, and half of her sons are sick. There are X-linked dominant X-linked recessive inheritance.

Genus of X-linked dominant inheritance (Fig. 1.125). This type of inheritance is characterized by:

1) affected males pass on their disease to daughters, but not to sons;

2) affected heterozygous women transmit diseases to half of their children, regardless of their gender;

3) Affected homozygous females transmit the disease to all their children.

This type of inheritance is not common. The disease in women is not as severe as in men. It is rather difficult to distinguish between yourself X-linked dominant and autosomal dominant inheritance. The use of new technologies (DNA probes) helps to more accurately identify the type of inheritance.

Rice. 1.125. X-linked dominant inheritance.

Rodovid X-linked recessive inheritance (Fig. 1.126). This type is characterized by such inheritance patterns:

1) almost all affected are men;

2) the trait is transmitted through a heterozygous mother who is phenotypically healthy;

3) the affected father never transmits the disease to his sons;

4) all daughters of the sick father will be heterozygous carriers;

5) a carrier woman passes the disease on to half of her sons, none of the daughters will be sick, but half daughters - carriers of the hereditary gene.

Rice. 1.126. X-linked recessive inheritance.

More than 300 traits are caused by mutant genes located on the X chromosome.

An example of recessive inheritance of a sex-linked gene is hemophilia. The disease is relatively common in men and very rare in women. Phenotypically healthy women are sometimes "carriers" and, when married to a healthy man, give birth to sons with hemophilia. Such women are heterozygous for a gene that causes the loss of the ability to blood clot. From marriages of men with hemophilia to healthy women, healthy sons and carrier daughters are always born, and from marriages of healthy men to carrier women, half of the sons are sick and half of the daughters are carriers. As already noted, this is due to the fact that the father passes on his X chromosome to his daughters, and the sons receive from the father only Y -chromosome, which never contains the hemophilia gene, while their only X chromosome comes from the mother.

The following are the main diseases that are inherited in a recessive, sex-linked type.

Agammaglobulinemia, albinism (some forms), hypochromic anemia, Wiskott-Aldrich syndrome, Hutner's syndrome, hemophilia A, hemophilia B, hyperparathyroidism, type VI glycogenosis, lack of glucose-6-phosphate dehydrogenase, nephrogenic diabetes insipidus, ichthyosis, Lowe's syndrome, Peltzius disease Merzbacher, periodic paralysis, retinitis pigmentosa, pseudohypertrophic form of myopathy, Fabry's disease, phosphate diabetes, Scholz's disease, color blindness (Fig. 1.127).

Rice. 1.127. Test for determining color perception with Rabkin tables.

Content

The science of heredity has long been considered something akin to charlatanism. It is no coincidence that even in the middle of the 20th century, genetics was considered a pseudoscience, and in the USSR its representatives were persecuted. Later, everything fell into place, genetics took pride of place among the fundamental sciences that study the living and plant world. The genealogical method is one of the varieties of genetic research: the genealogy of a person is studied, which helps to identify a tendency to inherit hereditary traits.

What is the genealogical method of research

The method of analyzing the pedigree was outlined at the end of the 19th century by F. Galton, later G. Yust gave uniform symbols when compiling family tree. The essence of the study is the compilation of a detailed pedigree of a person and its subsequent analysis in order to identify certain signs that members of the same family are committed to, as well as the presence of hereditary diseases. New laboratory methods of research are now emerging, but the advice of a pedigree specialist is still used in medicine and applied science.

What is used for

In applied science, the genealogical method is used to study the principles of the distribution of various hereditary traits among members of the same family: freckles, the ability to roll the tongue into a tube, short fingers, fused fingers, red hair, a tendency to diabetes, a cleft lip, and so on. Moreover, several types of inheritance are distinguished - autosomal dominant, autosomal recessive, sex-linked.

In medicine, the clinical and genealogical method helps to identify the presence of pathological signs and the likelihood of their inheritance. Often the picture becomes clear even without additional research (analysis of placental fluid for the presence of genetic diseases). The main thing is to establish a hereditary trait and calculate the probability of its manifestation in future generations.

What is the essence of the genealogical method

The main tool of genealogical analysis is the collection of information about the individual and his family. With the help of compiling detailed pedigrees, it becomes possible to single out one or another hereditary trait. In medicine, this technique is called clinical-genealogical. The specialist studies pedigree connections and tries to identify hereditary traits, trace their presence in close and distant relatives. The genealogical method consists of two stages - the compilation of a pedigree and its detailed analysis.

Tasks

The main advantage of the genealogical method is its versatility. It is used in solving theoretical and practical problems, for example, in determining the probability of inheritance of certain diseases:

• identification of a genetic trait;
• establishing it as hereditary;
• determining the type of study and penetarity of the gene;
• calculation of the probability of its inheritance;
• determination of the intensity of the mutation process;
• compilation of genetic maps of chromosomes.

Goals

The main purpose of genealogical analysis in medicine is the diagnosis of hereditary pathologies. At the same time, the compilation of a pedigree is one of the stages of the study, which reveals the possibility of inheriting a certain genetic trait. We are talking not only about such hereditary features as red hair or short fingers, character anomalies, but also about serious diseases that can be inherited, for example, schizophrenia, cystic fibrosis or hemophilia.

Genetic analysis for hereditary diseases in pregnant women

Any couple who are expecting a child can turn to a geneticist to find out if their unborn child has any genetic abnormalities. In some cases, consultation with a geneticist is mandatory:

• age of parents (more than 35 years for the mother and 40 years for the father);
• the family already has children with genetic diseases;
• unfavorable living conditions of one of the parents (bad environment, alcohol and drug abuse);
• the mother suffered a serious infectious disease during her illness;
• one of the parents has a mental illness;

Professional genealogical research is one of the types of genetic research that is carried out for future parents. Other methods of studying human heredity include:

• ultrasound diagnostics;
• study amniotic fluid(amniocentesis);
• research on the subject possible consequences after infections transferred during pregnancy (placentocentesis);
• genetic study of cord blood (cordocentesis).

Stages of the genealogical method

When compiling a pedigree and its subsequent analysis, the geneticist acts in stages. There are three main ones:

1. A proband is determined for which a detailed pedigree is compiled. When expecting a child, the proband is almost always the mother, in other cases it is the carrier of a hereditary trait.
2. Drawing up a pedigree, while collecting an anamnesis of the proband and his family ties.
3. Analysis of the pedigree and conclusion about the probability and type of inheritance of the trait.

Drawing up a pedigree

In medical genetic counseling, a proband is taken as the basis - a person who is presumably a carrier of a hereditary trait or suffering from a genetic disease. The pedigree is compiled from the words of the subject, while for the accuracy of the picture it is necessary to collect information about three or even four generations of his family. In addition, experts interview the proband itself and conduct a visual examination for the presence and severity of a hereditary trait.

All information is recorded in the medical genetic card in the following order:

• information about the proband - the presence of a hereditary trait or genetic diseases, condition, obstetric anamnesis, mental anamnesis, nationality and place of residence;
• information about parents, brothers and sisters (siblings);
• information about relatives on the part of the mother and father.

Symbolism of the genealogical method

Genealogical tables use certain symbols that were developed in 1931 by G. Yust. The female gender in them is indicated by a circle, male - by a square. Some scholars use the "Mirror of Venus" (circle with a cross) for the feminine gender, and the "Shield and Spear of Mars" (circle with an arrow) for the masculine gender. Sibs are placed on the same line with the proband, generation numbers are shown in the form of Roman numerals, relatives of the same generation are shown in Arabic.

Genealogical analysis

The use of pedigree analysis helps to identify a hereditary trait, usually pathological. This is established if it occurs more than twice in several generations. After that, an assessment of the type of inheritance is carried out (autosomal recessive, autosomal dominant, or sex-linked). Further, there are conclusions about the likelihood of the appearance of a hereditary trait in children of members of the pedigree and, if necessary, an indication for referral for additional genetic studies.

The hereditary nature of the trait

The autosomal dominant type of inheritance is determined with the complete dominance of the trait, these include eye color, freckles, hair structure, etc. In case of illness:

• inheritance goes equally at women and men;
• there are patients vertically (in generations) and horizontally (brothers and sisters);
• sick parents have a high probability of inheriting a pathological gene;
• with a large parent, the risk of inheritance is 50%.

Autosomal recessive type:

• siblings are carriers horizontal line;
• in the pedigree of silent carriers among the relatives of the proband;
• the mother and father of the carrier are healthy, but may be carriers of the recessive gene, while the probability that the child will inherit the pathological recognition is 25%.

There is a type of heredity linked to sex:

• dominant X-linkage - manifests itself in both sexes, but is transmitted through the female line;
• recessive X-linkage - is transmitted only to men from mothers, and daughters will be healthy, and sons will be sick with different probability;
• Y-linked (hollandric) - transmitted through the male line;

Type of inheritance and gene penetrance

Determination of linkage groups and mapping of chromosomes

Study of the mutation process

Clinical pedigree analysis studies the variability of mutational processes, and the method is useful in analyzing the occurrence of "atypical" or "spontaneous" mutations, such as Down's syndrome. The difference between episodic mutations and regular gene processes within the same family is studied. The following mutation factors are considered:

• the occurrence of a mutation;
• the intensity of the process;
• factors that contributed to the emergence.

Gene Interaction Analysis

During the medical genealogical analysis, the processes of gene interaction are revealed, which help to decipher the conditionality of the appearance of pathological hereditary traits within the same family. A carefully developed pedigree becomes the foundation for further studies of the intensity of the development of gene mutations, identifying the type of inheritance and the likelihood of obtaining a gene from the heirs of the proband.

Homo and heterozygosity of parents

The totality of hereditary traits passes to us from our parents. A gene received from both parents will be called homozygous. If mother and father curly hair, then the gene responsible for the structure of the hair is determined to be homozygous. If the mother has straight hair and the father has curly hair, then the hair structure gene is determined to be heterozygous. A child may have a homozygous eye color gene and a heterozygous hair color gene. In the case of complete dominance of the gene, the trait is inherited with almost 100% probability along the vertical line.