Genealogical method introduced at the end of the 19th century. Francis Galton. It is based on constructing pedigrees and tracing the transmission of a certain trait through a series of generations.
This method is applicable if direct relatives are known - ancestors owner of a hereditary trait ( proband ) on the maternal and paternal lines in a number of generations or in the case when known descendants the proband also spans several generations.
Accepted notation system in the pedigrees of the person that was proposed G. Yust in 1931. Generations are designated by Roman numerals, individuals in a given generation are designated by Arabic numerals.
Stages of genealogical analysis:
1) collection of data about all relatives of the subject (history);
2) building a pedigree;
3) analysis of the pedigree and development of a conclusion.
The difficulty of collecting anamnesis lies in the fact that the proband must know well, if possible, most of his relatives and their state of health.
The method allows you to set:
1) whether this trait is hereditary;
2) type and nature of inheritance;
3) zygosity of persons in the pedigree;
4) gene penentrance;
5) the likelihood of having a child with this hereditary pathology.
Types of inheritance:
1.Autosomal dominant
1) patients in each generation;
2) a sick child with sick parents;
4) inheritance goes vertically and horizontally;
5) probability of inheritance 100%, 75% and 50% (AA×AA, AA×aa, AA×Aa; Aa×Aa; Aa×aa).
It should be emphasized that the above signs of an autosomal dominant type of inheritance will only appear with complete dominance. This is how polydactyly (six-fingered feet), brachydactyly, chondrodystrophic dwarfism, cataracts, freckles, curly hair, brown eye color, etc. are inherited in humans. With incomplete dominance hybrids will exhibit an intermediate form of inheritance. With incomplete penetrance gene patients may not be present in every generation.
2.Autosomal recessive the type of inheritance is characterized by the following features:
3) men and women are affected equally;
4) inheritance occurs predominantly horizontally;
5) probability of inheritance 25%, 50% and 100%.
Most often, the probability of inheritance of an autosomal recessive type is 25%, since due to the severity of the disease such patients either do not live to childbearing age or do not marry. This is how humans are inherited phenylketonuria , sickle cell anemia, albinism, red hair, blue eyes, etc.
3.Sex-linked recessive the type of inheritance is characterized by the following features:
1) patients are not in every generation;
2) healthy parents have a sick child;
3) predominantly men are affected;
4) inheritance occurs mainly horizontally;
5) the probability of inheritance is 25% for all children and 50% for boys.
This is how humans are inherited hemophilia , color blindness, hereditary anemia, Duchenne muscular dystrophy, etc.
4.Sex-linked dominant the type of inheritance is similar to autosomal dominant, except that the man passes this trait on to all his daughters (sons receive a Y chromosome from their father, they are healthy). An example of such a disease is a special form of rickets that is resistant to treatment with vitamin D ( vitamin D – resistant rickets ). Men are more seriously ill. 2 more similar diseases: keratosis pilaris (accompanied by complete loss of hair, eyelashes, eyebrows) and pigmentary dermatosis .
5.Holandric the type of inheritance is characterized by the following features:
1) patients in all generations;
2) only men get sick;
3) a sick father has all his sons sick;
4) 100% probability in boys.
This is how humans are inherited ichthyosis of the skin , hair growth of the external auditory canals and middle phalanges of the fingers, membranes between the toes, etc. Holandric characteristics are not significant in human hereditary pathology. There are also pathological mutations that disrupt the formation of testes and spermatogenesis, but they are not inherited (their carriers are sterile).
The use of the genealogical method also showed that the probability of occurrence deformities, stillbirths, early mortality in offspring consanguineous marriages significantly higher than in unrelated ones. This can be explained by the fact that relatives have the same genes more often than non-relatives, and therefore, in related marriages, homozygous combinations , including recessive genes that determine certain anomalies.
Here is an example of identifying a pathological recessive trait in a consanguineous marriage. From two related marriages, 4 out of 8 children appeared in one family, and in the other - 2 out of 5, suffering hereditary amaurotic idiocy (damage to the central nervous system). One of the two common ancestors passed the recessive gene through three generations to each of the four parents.
The genealogical method is also widely used as a method for diagnosing diseases with a hereditary nature, which is of great importance for medical genetic consultations, when people interested in the health of their offspring raise a question with the doctor about the fear of having sick offspring.
Twin method
Twin method the study of human genetics introduced into medical practice F. Galton in 1876. It allows us to determine the role of the genotype and environment in the manifestation of traits.
Gemini are called simultaneously born individuals in single-bearing animals (humans, horses, cattle, etc.).
There are mono- and dizygotic twins. Monozygotic (identical), identical twins develop from one fertilized egg (the phenomenon of polyembryony). Monozygotic twins have exactly the same genotype and, if they differ phenotypically, this is due to the influence of environmental factors.
Dizygotic(fraternal or fraternal) twins develop after fertilization by sperm of several simultaneously matured eggs. Twins have different genotypes, and their phenotypic differences are determined by both genotype and environmental factors.
Monozygotic twins have a high degree of similarity in characteristics, which are determined mainly by genotype. For example, monozygotic twins are always the same sex, they have the same blood groups according to different systems (AB0, Rh, MN, etc.), the same eye color, the same type of dermatoglyphic indicators on the fingers and palms, etc.
The percentage of similarity of a group of twins on the characteristic being studied is called concordance , and the percentage difference is discordance . Since monozygotic twins have the same genotype, their concordance is higher than that of dizygotic twins.
To assess the role of heredity and environment in the development of a particular trait, they use Holzinger's formula :
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where H is the heritability of the trait, KMB% is the concordance of monozygotic twins, KDB% is the concordance of dizygotic twins.
In humans, twins are most often encountered, triplets are less common, quadruplets are even less common, and quintuplets are very rare. Statistics show that quintuplets are born approximately once every 54 million births, gears ~ every 5 billion births, and septuplets are even more rare. On average, the birth rate of twins is close to 1% and 1/3 of them are twins.
For the use of twins in genetic research, it is very important to accurately determine twin type . Diagnosis is made based on several criteria : 1) OBs must be of the same sex, RBs can be either the same sex or different sexes; 2) the presence of similarity (concordance) in OB and dissimilarity (discordance) in RB for many characteristics, including blood groups; However, it is necessary to take into account that during intrauterine life developmental disorders, somatic mutations, etc. may occur in one of the OBs, which can lead to some differences between the partners; 3) decisive, but difficult to implement criterion - reciprocal tissue transplantation in OB it is as successful as autotransplantation; in RB it is impossible due to immunological incompatibility.
Human twins are an excellent material for developing a general biological and very important practical problem: about the role of heredity and environment in the development of traits.
The OB pair has the same genotype, the RB pair has a different genotype. For both partners of the same pair of OB or RB, the external environment may be either the same or different.
Development comparison ABOUT V the same environment and different environment makes it possible to judge the influence of the environment on traits.
Development comparison ABOUT And RB V the same environment makes it possible to clarify the role of heredity in the development of traits.
4. Population-statistical method
Population-statistical The method of studying human genetics is based on the use of the Hardy-Weinberg law. It allows you to determine the frequency genes And genotypes in human populations. For example, homozygotes for the HbS gene are practically never found in Russia, but in West African countries their frequency varies: from 25% in Cameroon to 40% in Tanzania.
Study of the distribution of genes among the population of different geographical zones ( genogeography ) makes it possible to establish the centers of origin of various ethnic groups and their migration, to determine the degree of risk of hereditary diseases in individuals.
The basic laws of heredity established for living organisms are universal and fully valid for humans. However, as an object of genetic research, humans have their advantages and disadvantages.
It is impossible for people to plan artificial marriages. Back in 1923 N.K. Koltsov noted that “...we cannot conduct experiments, 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 targeted sampling from a large number of marriage pairs of those that correspond to the goals of this genetic study.
The large number of chromosomes - 2n=4b - significantly complicates the possibilities of human genetic analysis. However, the development of the latest methods of working with DNA, the method of somatic cell hybridization and some other methods eliminate this difficulty.
Due to the small number of descendants (in the second half of the 20th century, most families had 2-3 children), it is impossible to analyze splitting in the offspring of one family. However, in large populations it is possible to select families with characteristics of interest to the researcher. In addition, in some families certain characteristics have been traced over many generations. In such cases, genetic analysis is possible. Another difficulty is associated with the duration of generational change in humans. One human generation takes an average of 30 years. And, therefore, a geneticist cannot observe more than one or two generations.
Humans are characterized by large genotypic and phenotypic polymorphism. The manifestation of many signs and diseases is highly dependent on environmental conditions. 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, the human environment also includes 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. Thus, the global international program “Human Genome” has as its task the study of 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 genetic. Let's take a closer look at each of them.
Considered one of the main methods in human genetics, this method is based on genealogy - the study of pedigrees. 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 widely used to solve both scientific and applied problems. It allows you to identify the hereditary nature of a 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 the penetrance of alleles. The genealogical method underlies medical genetic counseling. It includes two stages: compilation of pedigrees and their genealogical analysis.
Drawing up a pedigree. Gathering information about the family begins with a person called the proband. Usually this is a patient with the disease being studied. Children of the same parental pair are called sibs (siblings). In most cases, a pedigree is collected based on one or more characteristics. Pedigree can be complete or limited. The more generations traced in a pedigree, the more complete it is and the higher the chances of obtaining completely reliable information. The collection of genetic information is carried out through interviews, questionnaires, and personal examination of the family. The survey usually begins with maternal relatives: maternal grandparents, indicating grandchildren, children of each child of the grandparents. The pedigree includes information about miscarriages, abortions, stillbirths, infertile marriages, etc.
When compiling a pedigree, a brief record of data is kept about each member of the clan, indicating his relationship in relation to the proband. Usually the following are indicated: last name, first name and patronymic, date of birth and death, age, nationality, place of residence of the family, profession, presence of chronic diseases in the family, cause of death of the deceased, etc.
After collecting information, a graphical representation of the pedigree is drawn up using a system of symbols (Fig. 2.1).
When performing this work, it is important to observe the following rules:
1. Compilation of a pedigree begins with the proband. Siblings are arranged in order of birth from left to right, starting with the eldest.
2. All members of the pedigree are arranged strictly by generation in one row.
3. Generations are indicated by Roman numerals to the left of the pedigree from top to bottom.
4. Arabic numerals are used to 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 graphical representation of the pedigree can be vertical-horizontal or arranged in a circle (in the case of extensive data). The pedigree diagram is accompanied by a description of the symbols under the picture, which is called a legend (Fig. 2.2).
Genetic pedigree analysis
The task of genetic analysis is to establish the hereditary nature of the disease and the type of inheritance, identify heterozygous carriers of the mutant gene, as well as predict the birth of sick children in families with hereditary pathology.
Pedigree analysis includes the following steps: 1. Determining whether a given trait or disease is isolated in the family or whether there are several cases (familial). If a trait occurs several times in different generations, then we can assume that this trait is hereditary in nature. 2. Determination of the type of inheritance of a trait. To do this, analyze the pedigree, taking into account the following points:
1) whether the studied trait occurs in all generations and how many members of the pedigree possess it;
2) is its frequency the same in both sexes and in which sex is it more common;
3) to persons of which gender the trait is transmitted from a sick father and a sick mother;
4) are there 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 inheritance features 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 on the mutant gene to daughters and sons. Transmission of the disease from father to son is possible.
Clinical manifestations of the disease can vary significantly depending on the expressivity and penetrance of the gene. Expressiveness is the degree of expression of a gene (in our case, the severity of the disease). With high gene expression, a severe, often fatal form of the disease develops; with 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 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 mutant 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 rarely encountered in the pedigree and not in all generations. The likelihood of the disease is the same in girls and boys. The symptom can appear in children whose births were healthy, but were heterozygous carriers of the mutant gene. There are several options for such marriages:
1) mother aa x father aa - all children of such parents will be sick (aa);
2) mother Aa x father aa - 50% of 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. Polydactyly (six-fingered), brachydactyly (short-fingered), achondroplasia (dwarfism), Marfan syndrome ("spider fingers") and other diseases are inherited in an autosomal dominant manner (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 there are often cases when carriers of a dominant gene remain phenotypically healthy. As a result, the type of pedigree changes and generation gaps appear.
Carriage of a dominant gene without phenotypic manifestation can be suspected in one of the parents if among his descendants there are patients with the same dominant pathology. When healthy parents have a sick child and there are other cases of this disease in the pedigree, it is reasonable to assume that one of the patient’s parents had a defective gene that did not penetrate, but was passed on to the descendant.
A dominant gene may have varying degrees of expressivity, which makes it difficult to establish an autosomal dominant mode of inheritance. Let's consider this using the example of a hereditary connective tissue pathology - Marfan 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 impact on the offspring, as evidenced by the fact that mental retardation among children from consanguineous marriages is 4 times higher than in families with unrelated marriages.
With an autosomal recessive type of inheritance (as with an autosomal dominant one), varying degrees of expressivity 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.
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 localized on the X chromosome. Genes located on chromosome X can be recessive or dominant.
In women, the mutant gene may be located on both X chromosomes or only on 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 on only to daughters and never to sons. Any gene, both dominant and recessive, localized on its X chromosome will necessarily manifest itself. This is the main feature of X-linked inheritance.
X-linked recessive inheritance is characterized by the following features:
1) the disease occurs more often 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 only be born in families where the father is sick and the mother is heterozygous for the mutant gene.
Let's 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 the daughters will receive one X chromosome with a mutant gene from their father and will be heterozygous carriers (since they will receive a second normal X chromosome from their mother) . If a healthy man and a woman who is a carrier of a pathological gene marry, the probability of having a sick boy will be 50% of all boys and 25% of all children.
The probability of giving birth to 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 develop 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 insufficient levels of blood clotting factors in the blood. In 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). From this we can assume that the hemophilia gene is sex-linked. Sick children are more often born from healthy parents and, therefore, the disease gene is recessive.
Hemophilia is known to be widespread among the royal families of Europe. This is due to consanguineous marriages. As a result, the resulting mutations remained 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 Woldemar and Henry of Prussia, Frederick of Hesse, Tsarevich Alexei Romanov, Ruprecht of Texas, two Battenberg and two Spanish princes (Figure 2.6). In addition to hemophilia, the X chromosome contains recessive genes that cause Duchenne myopathy, some forms of color blindness and other diseases.
When a dominant gene is localized on chromosome X, the type of inheritance is called X-linked dominant. It is characterized by the following symptoms:
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 each generation;
3) if a father is sick, then all his daughters will be sick, and all his sons will be healthy;
4) if the mother is sick, then the probability of giving birth to 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 their children healthy.
Phosphatemia (lack of phosphate in the blood), brown coloration of tooth enamel, etc. are inherited according to the X-linked dominant type.
Y-linked inheritance also has its own characteristics.
Few genes are localized on the Y chromosome in men. They are passed on only to sons and never to daughters (Holandric inheritance). With the Y chromosome, men inherit such characteristics as hypertrichosis (the presence of hair along the edges of the ears), skin membranes between the toes, the development of the testes, the intensity of growth of the body, limbs and teeth. Characteristic features of inheritance with the Y chromosome can be seen in Fig. 2.7.
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 teaching methods of an activity-based nature, which meets the new requirements of the Federal State Educational Standard. In the process of professional training, a student independently has to find individual theoretical calculations from a large number of scientific, methodological and specialized literature, as well as independently conduct instrumental and laboratory studies with subsequent analysis of the results obtained.
When conducting UIRS, students develop 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 assumptions, conduct research, analyze results, draw conclusions, etc. d).
UIRS is the 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 manual for the compilation and analysis of pedigrees. Educating students on genealogy issues, developing 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
Currently, according to the World Health Organization, about 10 thousand hereditary diseases are known, which are becoming increasingly important in the general pathology of humans. Harmful gene mutations are considered the main cause of hereditary diseases. Medical genetics is the study of hereditary human diseases. To diagnose hereditary pathology in medical genetics, the genealogical method is used. This method is accessible and informational; it makes it possible to establish the hereditary nature of the disease, the type of transmission of the defective gene, and trace the possible risk of its manifestation in close relatives.
The choice of topic was due to my interest in studying the pedigree of my family, since frequently recurring diseases are noted in our family, there was a need to study its hereditary nature.
Purpose of the study: the use of the genealogical method to identify hereditary diseases in the family.
Object of study: pedigree of the Kovalchuk family of Elena Igorevna on her mother’s side.
Research objectives:
- Analyze the scientific basis of the genealogical method.
- Through the practical application of the method, compile a family pedigree.
- Conduct a pedigree analysis to identify the nature and type of inherited traits.
- Develop a guide to compiling and analyzing pedigrees.
Mresearch methods: study and analysis of general and specialized literature, observation, interview method, qualitative analysis of pedigree.
Practical significance: Training in the skills of compiling and analyzing a pedigree. Development of a manual for the compilation and analysis of pedigrees. Educating students on genealogy issues.
Chapter 1. Genealogical method of studying human heredity
Thus, the genealogical method is widely used in solving theoretical and applied problems: establishing the hereditary nature of a trait; determination of the type of inheritance of the disease. Determine the prognosis of the disease and calculate the risk for offspring.
In the genealogical method, 2 stages can be distinguished: Stage 1 – compilation of pedigrees; Stage 2 – using genealogical data for genetic analysis.
Chapter 2. Compilation and analysis of the pedigree
Thus, compiling a pedigree taking into account the basic rules and requirements will allow us to successfully conduct a qualitative analysis of the pedigree, which in turn will provide the most complete information about the nature and type of the inherited trait, and will also determine the likelihood of transmitting the trait to subsequent generations.
Chapter 3. Criteria for types of inheritance
Thus, having studied the criteria for types and features of inheritance of traits, it becomes possible to more accurately establish the nature of inheritance of traits in the pedigree being studied and assume the likelihood of the gene manifesting itself in subsequent generations
Chapter 4. Pedigree and its analysis
4.1 Drawing up a pedigree
In order to identify the presence of inherited diseases in the family, a pedigree was compiled, taking into account the basic requirements ( Application).
A “pedigree legend” has been defined, which includes: a brief record with an accurate description of family members and his relationship with the proband, information about the health status of pedigree members, information about the nature of inheritance of the disease and the characteristics of its manifestation, the onset and nature of the course of the disease, and 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 determine whether the trait is inherited, and also to understand the nature of 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 in the vertical direction, one case of tonsillitis is noted - this indicates the hereditary nature of the trait, since these are repeated 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 inheritance of the trait.
This type of inheritance confirms the fact that in the second generation the disease did not manifest itself, 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 pedigree analysis made it possible to establish:
- The nature of the inherited trait is a hereditary predisposition to a decrease in the immune response to the causative agent of tonsillitis;
- Determine the type of inherited trait as autosomal dominant.
- Assume that subsequent generations from the proband can inherit this trait.
- To avoid an increase in the severity of pathological disorders in subsequent generations, it is necessary to carry out preventive measures.
Conclusion
This study was aimed at using the genealogical method to identify hereditary diseases in the family.
Special literature has been studied on this issue, the content of which reflects the scientific basis of the genealogical method. Theoretical study of the issue indicates the relevance of studying human genetics in connection with the increasing occurrence 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, since it is the most informational, and also accessible to any person interested in the history of the development of their family or clan, including the presence of hereditary diseases in the clan.
In the process of applying the genealogical method in practice, a pedigree was compiled and its qualitative analysis was made. The analysis results showed:
- The presence in the family of a hereditary predisposition to tonsillitis, which is based on a decrease in the immune response to the pathogen.
- Predisposition to the disease is transmitted along the female vertical line.
- Inheritance of the trait belongs to the autosomal dominant type of inheritance.
- With this type of inheritance of the trait, an increase in the severity of pathological disorders in subsequent generations is characteristic.
Thus, analysis of the pedigree makes it possible 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, since it made it possible to determine the nature and type of inheritance of a trait and to assume the risk for future generations. It remains the most accessible and informative method in diagnosing genetic diseases.
In the course of the work, based on the results of the study, it was established that the manifestation of genetic diseases, as well as reducing the increase in the severity of pathological disorders in subsequent generations, can be avoided by implementing preventive measures.
Compliance with recommended preventive measures that ensure 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 transmitting the mutant gene to subsequent generations.
Thus, a healthy lifestyle is the key to preventing the manifestation of not only non-hereditary, but also genetic diseases in humans.
Human genetics is a science that studies, in addition to heredity and variability, the formation of normal human characteristics.
Subject are normal human characteristics.
Problems of genetics:
Studying the patterns of genetic determination of human traits
Study of the material structure of gene inheritance
Study of the organization of information flow in human cells
Analysis of the nature of interaction between genes in the process of character formation
Studying the influence of environmental factors on human heredity
History of the development of human genetics.
1815 Adams"Philosophical treatise on the hereditary properties of the human race." 1 reference book about genetics.
1866 Florensky"Improvement and Degeneration of the Human Race"
Influence of the external environment
The influence of consanguineous marriages
Galton – founder of genetics methods: genealogical, twin, statistical.
Garred. Alkaptonuria is a degenerate metabolic error, a recessive disease (biochemical genetics - the beginning of development).
Yu.A. Giritienko – head of the first department of genetics in Petrograd in 1919.
1932 – 37. The first medical genetic institute was opened in Moscow under the leadership Levikha.
Scientists played a big role Hardy and Weinberg=>main principles of population stability.
Features of genetic analysis in humans.
Bisocial human nature. The formation of any trait is influenced by environmental factors and the social environment in which a person lives.
Impossibility of direct experiments
Impossibility of using the hybridological method
Late onset of puberty => longer life span of one generation
Small number of descendants
Large number of chromosomes (46)
The impossibility of creating identical and strictly controlled living conditions for descendants
The essence of the genealogical method and the problems solved with its help in human genetics.
The genealogical method is a method of compiling a pedigree. In medicine – clinical and genealogical.
It is based on compiling a person’s pedigree and studying the nature of inheritance of a trait. This method was first proposed by F. Galton in 1865. This is the oldest method. Its essence is to establish pedigree relationships and determine dominant and recessive traits and the nature of their inheritance. This method is especially effective when studying gene mutations.
Establishing the hereditary nature of a trait
Determining the type of inheritance of a trait
Gene linkage analysis and chromosome mapping
Study of the intensity of the mutation process
Deciphering the mechanisms of gene interaction
Use of this method in medical genetic counseling
The principles of constructing genealogies and the symbolism used in this.
Proband – a person who has contacted a geneticist for advice
Sibs - siblings of the proband
The use of this method is possible when direct relatives are known - the ancestors of the owner of the hereditary trait ( proband) on the maternal and paternal lines in a number of generations or the descendants of the proband also in several generations. When compiling pedigrees in genetics, a certain notation system is used. After compiling the pedigree, it is analyzed in order to establish the nature of inheritance of the trait being studied.
Conventions adopted when compiling pedigrees: 1 - man; 2 - woman; 3 - gender is unknown; 4 - owner of the trait being studied; 5 - heterozygous carrier of the recessive gene being studied; 6 - marriage; 7 - marriage of a man with two women; 8 - consanguineous marriage; 9 - parents, children and their order of birth; 10 - dizygotic twins; 11 - monozygotic twins.
Thanks to the genealogical method, the types of inheritance of many traits in humans have been determined. Thus, the autosomal dominant type inherits polydactyly (increased number of fingers), the ability to curl the tongue into a tube, brachydactyly (short fingers due to the absence of two phalanges on the fingers), freckles, early baldness, fused fingers, cleft lip, cleft palate, eye cataracts, bone fragility and many others. Albinism, red hair, susceptibility to polio, diabetes mellitus, congenital deafness and other traits are inherited as autosomal recessive.
The twin method, its essence and problems solved with its help in human genetics.
The twin method is based on the study of the phenotype and genotype of twins to determine the degree of environmental influence on the development of various traits. This method was proposed in 1876 by the English researcher F. Galton to differentiate the influence of heredity and environment on the development of various traits in humans. The twin method allows you to determine the degree of manifestation of a trait in a couple, the influence of heredity and environment on the development of traits. All differences that appear in identical twins who have the same genotype are associated with the influence of external conditions. Of great interest are cases where such a couple was separated for some reason in childhood and the twins grew up and were brought up in different conditions. The study of fraternal twins allows us to analyze the development of different genotypes under the same environmental conditions. The twin method made it possible to establish that for many diseases the environmental conditions under which the phenotype is formed play a significant role. For example, such characteristics as blood type, eye and hair color are determined only by the genotype and do not depend on the environment. Some diseases, although caused by viruses and bacteria, depend to some extent on hereditary predisposition. Diseases such as hypertension and rheumatism are largely determined by external factors and, to a lesser extent, by heredity. Thus, the twin method allows us to identify the role of genotype and environmental factors in the formation of a trait, for which the degrees of similarity (concordance) and differences (discordance) of monozygotic and dizygotic twins are studied and compared.
Types of twins and their characteristics. Causes and frequency of twin births.
Among twins, there are identical and fraternal twins. Identical twins are formed from one zygote (monozygotic), which splits into two parts at an early stage of cleavage. In this case, one fertilized egg gives rise to not one, but two embryos at once. They have the same genetic material, are always the same sex, and are the most interesting to study. The similarity between these twins is almost absolute. Small differences may be explained by the influence of developmental conditions. Fraternal twins (non-identical, or dizygotic) are formed from different zygotes, as a result of the fertilization of two eggs by two sperm. They are no more similar to each other than siblings born at different times. Such twins can be same-sex or opposite-sex.
The overall incidence of twin births averages 1.1 – 1.2% of all births; of these, about 1/3 are monozygotic twins, and 2/3 are dizygotic twins. The incidence of monozygotic twins is similar across populations, but the incidence of dizygotic twins varies significantly across populations. For example, in the United States, dizygotic twins are born more often among blacks than among whites. In Europe, dizygotic twins occur at a rate of 8 per 1,000 births. The lowest frequency of birth of dizygotic twins is inherent in Mongoloid populations, where it is 2-2.5 per 1,000 births. The likelihood of having dizygotic twins increases with the age of the mother and the birth order of the children. This rule applies exclusively to dizygotic twins. The effect of maternal age is apparently explained by an increase in the level of follicle-stimulating hormone in women with age. Follicle-stimulating hormone is a hormone of the anterior pituitary gland that stimulates the formation of follicles in the ovaries, their growth and maturation, promotes the process of selecting a dominant follicle and the formation of mature graphite vesicles. An increase in the level of this hormone leads to more frequent polyovulation. This hypothesis is also confirmed by the facts of the increased frequency of multiple births in women undergoing treatment for infertility with the help of gonadotropic hormones. With regard to dizygotic multiple births, there are also facts indicating the influence of genetic factors on the likelihood of having twins.
The likelihood of having dizygotic twins is higher for those women whose relatives have already had twins. Perhaps the main genetically determined cause in this case may also be the level of gonadotropin. No such data are available for monozygotic twins. Due to the slightly increased mortality rate among twins compared to that of singletons, the proportion of twins in the population is only 0.9%. Such a low frequency of twins makes it difficult to select a sufficient number of pairs with the studied trait.
Assessing the role of genetic and environmental factors in the formation of qualitative and quantitative traits based on data from twin studies.
To assess the effectiveness of the influence of some external factors H + E = 1 H = Cmz – Cdz/100 – Cdz where H is a hereditary factor C – environmental factor Cmz – monozygotes Cdz – dizygotes If H = closer to 0 – environmental factors have a greater influence If H = 1 – 0.7 – genetic If H = 0.4 – 0.7 – more environmental than genetic
The essence of the population statistical method and the problems solved with its help in human genetics.
This is a method for studying the distribution of hereditary traits (hereditary diseases) in populations. An essential point when using this method is the statistical processing of the data obtained. A population is understood as a collection of individuals of the same species, living for a long time in a certain territory, freely interbreeding with each other, having a common origin, a certain genetic structure and, to one degree or another, isolated from other such collections of individuals of a given species. A population is not only a form of existence of a species, but also a unit of evolution, since the microevolutionary processes that culminate in the formation of a species are based on genetic transformations in populations.
A special branch of genetics deals with the study of the genetic structure of populations - population genetics.
One of the important areas in modern genetics is population genetics. It studies the genetic structure of populations, their gene pool, and the interaction of factors that determine the constancy and change in the genetic structure of populations. In genetics, a population is understood as a set of freely interbreeding individuals of the same species, occupying a certain area and having a common gene pool over a number of generations. (The gene pool is the entire set of genes found in individuals of a given population).
In medical genetics, the population statistical method is used in the study of hereditary diseases of the population, the frequency of normal and pathological genes, genotypes and phenotypes in populations of various localities, countries and cities. In addition, this method studies the patterns of distribution of hereditary diseases in populations of different structure and the ability to predict their frequency in subsequent generations.
The population statistical method is used to study:
a) the frequency of genes in the population, including the frequency of hereditary diseases;
b) patterns of the mutation process;
Heidi-Weinberg Law. Conditions for an ideal population.
To determine the frequency of occurrence of certain genes and genotypes, it is used Hardy-Weinberg law.
Hardy-Weinberg Law
In an ideal population, from generation to generation, a strictly defined ratio of the frequencies of dominant and recessive genes is maintained (1), as well as the ratio of the frequencies of genotypic classes of individuals (2).
p + q = 1, (1) R 2 + 2pq + q 2 = 1, (2)
Where p- frequency of occurrence of the dominant gene A; q- frequency of occurrence of a recessive gene A; R 2 - frequency of occurrence of homozygotes by dominant AA; 2pq- frequency of occurrence of heterozygotes Ahh; q 2 - frequency of occurrence of homozygotes for the recessive ahh.
The ideal population is a sufficiently large, panmictic (panmixia - free crossing) population in which there is no mutation process, natural selection and other factors that disturb the balance of genes. It is clear that ideal populations do not exist in nature; in real populations, the Hardy-Weinberg law is used with amendments.
The Hardy-Weinberg law, in particular, is used to approximate the number of carriers of recessive genes for hereditary diseases. For example, phenylketonuria is known to occur at a frequency of 1:10,000 in this population. Phenylketonuria is inherited in an autosomal recessive manner, therefore, patients with phenylketonuria have the genotype ahh, that is q 2 = 0.0001. From here: q = 0,01; p= 1 - 0.01 = 0.99. Carriers of a recessive gene have a genotype Ahh, that is, they are heterozygotes. Frequency of occurrence of heterozygotes (2 pq) is 2 · 0.99 · 0.01 ≈ 0.02. Conclusion: in this population, about 2% of the population are carriers of the phenylketonuria gene. At the same time, you can calculate the frequency of occurrence of homozygotes by dominant ( AA): p 2 = 0.992, just under 98%.
A change in the balance of genotypes and alleles in a panmictic population occurs under the influence of constantly acting factors, which include: mutation process, population waves, isolation, natural selection, genetic drift, emigration, immigration, inbreeding. It is thanks to these phenomena that an elementary evolutionary phenomenon arises - a change in the genetic composition of the population, which is the initial stage of the process of speciation.
Give formulas for calculating the frequencies of genes and genotypes for erythrocyte isoantigens in the human population (AB0, Rh, MN).
Consider the case when one gene 0 recessive to the other two - A And IN, which are codominant with respect to each other. In a specific population we observe the following relationships:
|
Phenotype |
Genotype |
Genotype frequency |
|
r 2 |
||
|
p 2 + 2pr |
||
|
q 2 + 2pr |
||
Frequency estimation ( p, q, r) genes A, IN, 0 is carried out according to the well-known formulas of F. Bernstein as follows.
Finding preliminary estimates of gene frequencies 0 , A And IN:
r" = (0" ) 1/2 ;
p" = 1 - (A" + 0" ) 1/2 ; (6 )
q" = 1 - (B" + 0" ) 1/2 ;
Where 0" , A" And B"- frequencies of phenotypes, i.e. the ratio of the number of individuals with a certain phenotype to the sample size.
When the sum of preliminary gene frequencies does not equal 1, we introduce a correction D = 1 - (r" + p" + q").
r = (r" + 1/2D) (1 + 1/2D);
p = p" (1 + 1/2D);
q = q" (1 + 1/2D); (7 )
r + p + q = 1.
These formulas are valid for assessing the frequencies of AB0 blood group genes, as well as the system of taste sensitivity to RTS when identifying hypersensitive individuals in the group of examined individuals.
Biochemical method and its use in human genetics.
Allows you to detect metabolic disorders caused by changes in genes and, as a result, changes in the activity of various enzymes. Hereditary metabolic diseases are divided into diseases of carbohydrate metabolism (diabetes mellitus), metabolism of amino acids, lipids, minerals, etc.
Phenylketonuria is a disease of amino acid metabolism. The conversion of the essential amino acid phenylalanine to tyrosine is blocked, while phenylalanine is converted to phenylpyruvic acid, which is excreted in the urine. The disease leads to the rapid development of dementia in children. Early diagnosis and diet can stop the development of the disease.
The cause of many inborn errors of metabolism are various enzyme defects that arise as a result of mutations that change their structure. Biochemical indicators (primary gene product, accumulation of pathological metabolites inside the cell and in all cellular fluids of the patient) more accurately reflect the essence of the disease compared to clinical indicators, therefore their importance in the diagnosis of hereditary diseases is constantly increasing. The use of modern biochemical methods (electrophoresis, chromatography, spectroscopy, etc.) makes it possible to determine any metabolites specific to a particular hereditary disease.
The subject of modern biochemical diagnostics are specific metabolites, enzymopathies, and various proteins.
The objects of biochemical analysis can be urine, sweat, plasma and serum, blood cells, cell cultures (fibroblasts, lymphocytes).
For biochemical diagnostics, both simple qualitative reactions (for example, ferric chloride to detect phenylketonuria or dinitrophenylhydrazine to detect ketoacids) and more accurate methods are used.
The essence of the cytogenetic method and its application in human genetics.
The method is based on microscopic examination of the karyotype. A karyotype is a set of characteristics of the chromosome set of a somatic cell of an organism (shape of chromosomes, their number, size).
The cytogenetic method consists of a microscopic examination of the structure of chromosomes and their number in healthy and sick people. Of the three types of mutations, only chromosomal and genomic mutations can be detected under a microscope. The simplest method is express diagnostics - studying the number of sex chromosomes using X-chromatin. Normally, in women, one X chromosome is present in the cells in the form of a chromatin body, while in men such a body is absent. With sex pair trisomy, women have two bodies, and men have one. To identify trisomy in other pairs, the karyotype of somatic cells is examined and an idiogram is compiled, which is compared with the standard one.
In 1959, French scientists D. Lejeune, R. Turpin and M. Gautier established the chromosomal nature of Down's disease. In subsequent years, many other chromosomal syndromes commonly found in humans were described. Cytogenetics has become the most important branch of practical medicine. Currently, the cytogenetic method is used to diagnose chromosomal diseases, compile genetic maps of chromosomes, study the mutation process and other problems of human genetics.
In 1960, the first International Classification of Human Chromosomes was developed in Denver (USA). It is based on the size of the chromosomes and the position of the primary constriction - the centromere.
Dermatoglyphic method and its use in human genetics.
It is based on the study of the skin ridge patterns of the fingers and palms, as well as the flexor palmar grooves (2, 11). The nature of inheritance of the ridge count (the number of lines in the pattern on individual fingers) and papillary patterns are determined by the genotype, which makes it possible to diagnose a number of pathologies at the early stages of ontogenesis and determine their nature. The dermatoglyphic method in genetics was first proposed in 1892 by F. Galton. It was he who established that these patterns do not change throughout life and are an individual characteristic of a person. Galton clarified and supplemented the classification of the relief of skin patterns, the foundations of which were developed by Purkinje back in 1823. Later, F. Galton's classification was improved, and now it is widely used in forensics and genetic research. In 1939 Dermatoglyphs were described for the first time in Down syndrome. This study laid the foundation for the description of dermatoglyphs in other chromosomal diseases: Klinefelter syndrome, Shereshevsky-Turner syndrome, “cry of the cat” syndrome, which made it possible to use the methods of dermatoglyphics and palmoscopy in the diagnosis of these diseases. Specific deviations of these indicators are described in schizophrenia, myasthenia gravis, and lymphoid leukemia. Thus, modern science has a large arsenal of methods that allow us to obtain complete knowledge about human heredity and identify hereditary variability. However, a number of changes in human characteristics are of a non-hereditary nature and are modifications . They reflect changes in phenotype under the influence of environmental factors. The ability of an organism to vary the degree of variability of characteristics is called reaction norms . The body's reaction rate is determined by the genotype and can be broad or narrow. People differ, for example, in the norm of reaction to insolation - exposure to sunlight: the skin of some people acquires a dark tan, while the skin of others, with the same dose of radiation, gets burned. Residents of high mountains have hemoglobin levels 30% higher than residents of valleys. When climbing mountains, people's hemoglobin content increases as an adaptive adaptation to low oxygen levels; when returning to the valley, the hemoglobin content decreases again. Knowing the norm of the body's reaction allows us to select optimal conditions for the manifestation of certain signs and manage variability.
Molecular genetic method of human genetics.
They are associated with the isolation of DNA molecules from individual chromosomes, or mitochondria, with the subsequent study of the structure of these molecules, identifying changes in certain regions of the gene. This allows for molecular diagnostics of hereditary pathologies. The data obtained by these methods allows us to obtain a more complete picture of the human genome
The final result of molecular genetic methods is the identification of changes in certain sections of DNA, gene or chromosome. They are based on modern techniques for working with DNA or RNA. In the 70-80s. In connection with progress in molecular genetics and successes in the study of the human genome, the molecular genetic approach has found wide application.
The initial stage of molecular genetic analysis is obtaining DNA or RNA samples. For this purpose, genomic DNA is used (all
Cell DNA) or its individual fragments. In the latter case, in order to obtain a sufficient number of such fragments, it is necessary to amplify (multiply) them. To do this, they use the polymerase chain reaction, a fast method of enzymatic replication of a specific DNA fragment. It can be used to amplify any section of DNA located between two known sequences.
It is impossible to analyze huge DNA molecules in the form in which they exist in the cell. Therefore, first they need to be divided into parts and treated with various restriction enzymes - bacterial endonucleases. These enzymes are capable of cutting the DNA double helix, and the break sites are strictly specific to a given sample.
Methods of genetics of somatic cells.
The fact that somatic cells carry the entire volume of genetic information makes it possible to study the genetic patterns of the entire organism using them.
The method is based on the cultivation of individual human somatic cells and obtaining clones from them, as well as their hybridization and selection.
Somatic cells have a number of features:
They multiply quickly on nutrient media;
Easily cloned and produce genetically homogeneous offspring;
Clones can merge and produce hybrid offspring;
Easily subject to selection on special nutrient media;
Human cells are preserved well and for a long time when frozen.
Human somatic cells are obtained from different organs - skin, bone marrow, blood, embryonic tissue. However, connective tissue cells (fibroblasts) and blood lymphocytes are most often used.
Using the somatic cell hybridization method:
a) study metabolic processes in the cell;
b) identify the localization of genes in chromosomes;
c) study gene mutations;
d) study the mutagenic and carcinogenic activity of chemicals.
Using these methods, the heredity and variability of somatic cells are studied, which largely compensates for the impossibility of applying the method of hybridological analysis to humans.
Methods of genetics of somatic cells, based on the reproduction of these cells under artificial conditions, make it possible not only to analyze genetic processes in individual cells of the body, but, due to the usefulness of the hereditary material contained in them, to use them to study the genetic patterns of the entire organism.
In connection with the development in the 60s. XX century methods of genetics of somatic cells, humans were included in the group of objects of experimental genetics. Thanks to rapid reproduction on nutrient media, somatic cells can be obtained in quantities required for analysis. They are successfully cloned, producing genetically identical offspring. Different cells can fuse to form hybrid clones. They are easily selected on special nutrient media and can be preserved for a long time when deep frozen. All this allows the use of somatic cell cultures obtained from biopsy material (peripheral blood, skin, tumor tissue, embryonic tissue, cells from amniotic fluid) for human genetic research, which uses the following methods: 1) simple cultivation, 2) cloning, 3) selection, 4) hybridization.
Methods widely used in the study of human genetics include genealogical, population-statistical, twin, dermatoglyphics, cytogenetic, biochemical, and methods of somatic cell genetics.
Genealogical method
This method is based on the compilation and analysis of pedigrees. This method has been 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-bearing animals. Human genealogies have been compiled over many centuries regarding the reigning families of 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, which trace the transmission from generation to generation of a certain trait (disease), can replace the hybridological method, which is actually inapplicable to humans.
When compiling pedigrees, the starting point is the person - the 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 pedigree tables, the symbols proposed by G. Just in 1931 are used (Fig. 7.24). Generations are designated by Roman numerals, individuals in a given generation are designated by Arabic numerals.
Using the genealogical method, the hereditary nature of the trait being studied can be established, as well as the type
Rice. 7.24. Conventions when compiling pedigrees (according to G. Just) of its inheritance (autosomal dominant, autosomal recessive, X-linked dominant or recessive, Y-linked). When analyzing pedigrees for several characteristics, the linked nature of their inheritance can be revealed, which is used in the compilation of chromosomal maps. This method allows you to study the intensity of the mutation process, assess 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 significantly more complicated when families have few children.
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 greater or lesser probability depending on the genetic constitution of the parents (Fig. 7.25).
If a trait is analyzed that does not affect the viability of the organism, then 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 when there is a sufficient number of offspring in each vertical generation. When 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 rate 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 is also important to remember that some diseases do not appear immediately after birth.
Rice. 7.25. Probability of offspring with a dominant trait from different married couples (/ - III)
child. Many diseases inherited according to a dominant type develop only at a certain age. Thus, Huntington's chorea clinically manifests itself by the age of 35-40, and 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 transmission over a number of generations brachydactyly(short-fingered™). In Fig. Figure 7.26 shows a pedigree with this anomaly. In Fig. Figure 7.27 shows a pedigree with retinoblastoma in a case of incomplete penetrance.
Recessive traits appear phenotypically only in homozygotes for recessive alleles. These signs are usually
Rice. 7.26. Pedigree (X) with an autosomal dominant type of inheritance (brachydactyly - B)
Rice. 7.27.
Rice. 7.28. Probability of offspring with a recessive trait from different married couples
are found in the offspring of phenotypically normal parents who are carriers of recessive alleles. The probability of the appearance of recessive offspring in this case is 25%. If one of the parents has a recessive trait, then the likelihood of its manifestation in the offspring will depend on the genotype of the other parent. With recessive parents, all offspring will inherit the corresponding recessive trait (Fig. 7.28).
It is typical for pedigrees with an autosomal recessive inheritance pattern 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 increases in closely related marriages, where both parents may be carriers of the same recessive allele received from a common ancestor. An example of autosomal recessive inheritance is the pedigree of a family with pseudohypertrophic progressive myopathy, in which consanguineous marriages are common (Fig. 7.29). The horizontal spread of the disease in the last generation is noteworthy.
Genes located on the X chromosome and not having
Rice. 7.29. Pedigree with an autosomal recessive type of inheritance (pseudohypertrophic progressive myopathy) alleles on the Y chromosome are presented in genotypes of men and women in different doses. A woman receives her two X chromosomes and corresponding genes from both her father and mother, while a man inherits his only X chromosome only from his mother. The development of the corresponding trait in men is determined by the only allele present in his genotype, while in women it is the result of the interaction of two allelic genes. In this regard, traits inherited in an X-linked manner occur in a population with different probabilities in males and females.
With dominant X-linked inheritance, the trait is more common in women due to the greater possibility of them receiving the corresponding allele either from the father or from the mother. Men can only inherit this trait from their mother. Women with a dominant trait pass it on equally to daughters and sons, while men pass it on only to daughters. Sons never inherit a dominant X-linked trait from their fathers.
An example of this type of inheritance is the pedigree described in 1925 with follicular keratosis- skin disease accompanied by loss of eyelashes, eyebrows, and scalp hair (Fig. 7.30). A more severe course of the disease is typical in hemizygous men than in women, who are most often heterozygous.
In some diseases, the death of hemizygous males is observed in the early stages of ontogenesis. Then in the pedigrees among the affected there should be only women, in whose offspring the ratio of affected daughters, healthy daughters and healthy sons is equal to 1: 1: 1. Male dominant hemizygotes that do not die at very early stages of development are found in spontaneous abortions or among stillbirths. These features of inheritance in humans are characterized by pigmentary dermatosis.
A characteristic feature of pedigrees with this type of inheritance is the predominant manifestation of the trait in hemizygous men who inherit it from their mothers
Rice. 7.30. Pedigree with X-linked dominant inheritance (keratosis follicularis)
Rice. 7.31. Pedigree for X-linked recessive inheritance (hemophilia type A)
with a dominant phenotype who are carriers of a recessive allele. As a rule, the trait is inherited by men through generations from maternal grandfather to grandson. In women, it manifests itself only in a homozygous state, the likelihood of which increases with closely related marriages.
The best known example of recessive X-linked inheritance is hemophilia. The inheritance of hemophilia type A is presented in the pedigree of the descendants of Queen Victoria of England (Fig. 7.31).
Another example of inheritance by this type is color blindness- a certain form of color vision impairment.
The presence of the Y chromosome only in males explains the characteristics of the Y-linked, or holandric, 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. 7.32. Pedigree with Y-linked (holandric) type of inheritance
One trait whose Y-linked inheritance in humans is still debated is hypertrichosis of the auricle, or the presence of hair on the outer edge of the ear. It is believed that in addition to this gene, the short arm of the Y chromosome contains genes that determine male sex. In 1955, a Y chromosome-determined 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 antigen associated with the receptor activates the development of the gonad according to the male type (see section 3.6.5.2; 7.1.2).
This antigen has remained almost unchanged in the process of evolution and is found in the body of many animal species, including
and man. Thus, the inheritance of the ability to develop gonads according to the male type is determined by the holandric gene located on the Y chromosome (Fig. 7.32).