Hereditary diseases are human diseases caused by chromosomal and gene mutations. There are more than 6,000 of them. The terms “hereditary disease” and “congenital disease” are often mistakenly used as synonyms, however, congenital diseases are those diseases that are already present at the birth of a child and can be caused by both hereditary and exogenous factors during pregnancy.
If a mutation occurs in a cell at the early stages of ontogenesis, tissues will develop from it, all cells of which will carry this mutation. The earlier a somatic mutation occurs, the larger is the area of the body that carries the mutant trait. In humans, somatic mutations often lead to malignant tumors. Breast cancer is the result of somatic mutations In humans, somatic mutations often lead to the development of malignant tumors. Breast cancer is the result of somatic mutations Somatic mutations
Generative mutations 1. Monogenic - mutations in one gene The total frequency of gene diseases in the population is 1-2% The total frequency of gene diseases in the population is 1-2% Caused by mutations or the absence of individual genes and are inherited in full accordance with Mendel's laws Caused by mutations or the absence of individual genes and are inherited in full accordance with Mendel's laws Clinical manifestations arise as a result of the absence of certain genetic information, or the implementation of defective. Clinical manifestations arise as a result of the absence of certain genetic information, or the implementation of a defective one. Albinism
1.1 Autosomal dominant monogenic diseases The effect of the mutant gene is almost always The effect of the mutant gene is almost always Affected boys and girls are born with the same frequency. Sick boys and girls are born with the same frequency. The probability of developing the disease in the offspring is 50%. The probability of developing the disease in the offspring is 50%. It is based on a violation of the synthesis of structural proteins or proteins that perform specific functions (for example, hemoglobin) It is based on a violation of the synthesis of structural proteins or proteins that perform specific functions (for example, hemoglobin)
Hereditary connective tissue disease caused by multiple gene mutations, manifested by skeletal changes: tall stature with a relatively short body, long spider-like fingers (arachnodactyly), loose joints, often scoliosis, kyphosis, deformities chest(fossa or keel), arched sky. Eye damage is also common. Due to anomalies of the cardiovascular system, the average life expectancy has been reduced to 35 years. Morfan's syndrome
The high release of adrenaline, characteristic of the disease, contributes not only to the development of cardiovascular complications, but also to the appearance in some individuals of a special “fortitude” and mental endowment. Methods of treatment are unknown. It is believed that Paganini, Andersen, Chukovsky were ill with it Arachnodactyly - lengthening of the joints
A strange tribe of ostrich people (Sapadi) in Central Africa differs from other inhabitants of the Earth by an amazing property: they have only two fingers on their feet, and both are big! This is called the claw syndrome. It turned out that the first and fifth fingers were strongly developed on the foot, the second, third and fourth were completely absent (as if they should not have been at all!). This feature is fixed in the genes of the tribe and is inherited. Sapadis are excellent runners, they climb trees like monkeys, jumping from one tree to another. By the way, the gene that generates this syndrome is dominant, it is enough for one of the parents to have it, and the child will be born with deformity. claw syndrome
The mutant gene appears only in the homozygous state, and the heterozygous state is the so-called "carrier" Sick boys and girls are born with the same frequency. The probability of having a sick child is 25%. Parents of sick children may be phenotypically healthy, but are heterozygous carriers of the mutant gene Autosomal recessive inheritance is more typical for diseases in which the function of one or more enzymes is impaired, the so-called fermentopathy
Damage to a gene on chromosome 12. Accompanied by the accumulation of phenylalanine and its toxic products, which leads to severe damage to the central nervous system, manifested, in particular, in the form of a violation mental development. With timely diagnosis, pathological changes can be completely avoided if, from birth to puberty, the intake of phenylalanine with food is limited. Phenylketonuria The main thing is a strict diet! Late initiation of treatment, although it gives a certain effect, does not eliminate the previously developed irreversible changes in brain tissue.
Sickle cell anemia Red blood cells that carry hemoglobin S instead of normal hemoglobin A have a characteristic crescent shape (sickle-shaped) under the microscope, for which this form of hemoglobinopathy is called sickle cell anemia. Erythrocytes carrying hemoglobin S have reduced resistance and reduced oxygen-transporting ability S-hemoglobin A-hemoglobin
Progeria Progeria (Greek progērōs prematurely aged) is a pathological condition characterized by a complex of changes in the skin and internal organs caused by premature aging of the body
I started to get old, life is so short. For many people, it is like a river - Rushing somewhere in the alluring distance, Giving either joy, or sorrow, or sadness. Mine is like a rock with a waterfall That falls from the sky like a silver hail; That drop, which is given a second, Only to break on the rocks at the bottom. But there is no envy for the mighty river, Which flows smoothly along the path on the sand. Their fate is one, - having finished their wanderings, Find peace in the seas of compassion. Let my age be short, I'm not afraid of fate, After all, turning into steam, I'll return to heaven again. September 29, 2000 Alexander Bychkov Ashanti 7 years old with his mother.
Hemophilia Hemophilia is a hereditary disease characterized by decreased or impaired synthesis of blood coagulation factors. Usually men suffer from the disease, while women act as carriers of hemophilia. The most famous carrier of hemophilia in history was the English Queen Victoria, who passed the defective genes to two daughters and her son Leopold, and later to her grandchildren and great-grandchildren, including the Russian Tsarevich Alexei Nikolayevich, whose mother Tsarina Alexandra Feodorovna was a carrier of the hemophilia gene. Queen Victoria
Occur due to a change in the number or structure of chromosomes. Each disease has a typical karyotype and phenotype (for example, Down syndrome - trisomy 21, karyotype 47). Chromosomal diseases are much more common than monogenic ones and account for 12% of all mutations. They arise due to changes in the number or structure of chromosomes. Each disease has a typical karyotype and phenotype (for example, Down syndrome - trisomy 21, karyotype 47). Chromosomal diseases are much more common than monogenic ones and account for 12% of all mutations.
Examples of diseases Shereshevsky-Turner syndrome (lack of X in women - XO) Down's syndrome (trisomy 21-XXX) Klinefelter's syndrome (extra X in men - XXY) "Cat's cry" syndrome (loss of a fragment of the fifth chromosome) Patau syndrome (trisomy 13-XXX) Edwards syndrome (trisomy 18-XXX)
Down's syndrome A disease caused by an anomaly of the chromosome set (trisomy of 21 pairs of autosomes), the main manifestations of which are mental retardation, a peculiar appearance of the patient and congenital malformations. A transverse fold is often found on the palm. Frequency 1 per 700 newborns.
Loss of a fragment of chromosome 5. In this syndrome, a characteristic crying of a child is observed, resembling a cat's meow, the cause of which is a change in the larynx. The frequency of the syndrome is approximately 1: The sex ratio M1: F1.3. Cat's cry syndrome web-local.rudn.ru Patau's syndrome Polyhydramnios is a characteristic complication of pregnancy when carrying a fetus with Patau's syndrome: it occurs in almost 50% of cases. With Patau's syndrome (trisomy 13), severe congenital malformations are observed. web-local.rudn.ru
Diseases are caused by the polymeric nature of the interaction of genes or a combination of the interaction of several genes and environmental factors (multifactorial diseases). Polygenic diseases are not inherited according to the laws of Mendel. To assess the genetic risk, special tables are used for some malignant neoplasms, malformations, as well as a predisposition to coronary artery disease, diabetes mellitus and alcoholism, cleft lip and palate, congenital dislocation of the hip, schizophrenia, congenital heart defects wos-l.ru
There are 37 genes in mitochondrial DNA, they are involved in energy production, therefore, diseases associated with mutations in mitochondrial genes cause energy deficiency in cells. At conception, the embryo receives its mitochondria from the maternal egg (paternal ones die). 4. Mitochondrial mutations
Risk factors Physical factors (various types of ionizing radiation, ultraviolet radiation, electromagnetic radiation) Chemical factors (insecticides, herbicides, drugs, alcohol, certain drugs and other substances) Biological factors (pox, rubella, chickenpox, mumps, influenza, measles, hepatitis. A woman's age is over 35 years, consanguineous marriages, the presence of genetic diseases in the family).
At the antenatal clinic: Register at the antenatal clinic as soon as possible! Optimal - 6-10 weeks of pregnancy Perinatal screening of the 1st trimester - the thickness of the nuchal space of the fetus in weeks (normal up to 3 mm) and analysis of the level of blood hormones weeks: ultrasound and blood levels of hCG and AFP - the risk is calculated mathematically. Down, S. Edwards and neural tube defects of the week: high-quality ultrasound - visible anomalies in the development of the fetus Additional genetic consultation: Clinical and genealogical method - analysis of the nature of family ties, age of parents, presence of sick children Cytogenetic method - determination of changes in the chromosomal apparatus, prenatal diagnosis - analysis of amniotic fluid Biochemical method - analysis of blood and urine parameters for the diagnosis of hereditary metabolic diseases Prevention Taking a sample of amniotic fluid
Treatment Diet therapy Replacement therapy Removal of toxic metabolic products Influence on enzyme synthesis Exclusion of certain drugs (barbiturates, sulfonamides, etc.) Surgical treatment Today, a new method is being actively developed - gene therapy. With this method, defective genes can be replaced with "healthy" ones and the disease can be terminated by eliminating the cause (defective gene). Gene therapy
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Human genetic diseases are inherited.
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What is this? Hereditary diseases are so called because the "breakdown" affects the genetic material of a person, and, therefore, can be transmitted from generation to generation. Hereditary diseases caused by the presence of a defect in the genetic material.
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Types of gene mutations According to the level of damage to the hereditary material, all genetic diseases can be conditionally divided into chromosomal, in which there is a change (increase or decrease) in the number of chromosomes in the genome and monogenic (a change in the structure of one gene leads to the development of the disease).
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If a mutation occurs in any of the genes on the X chromosome of a woman, the disease may not manifest itself in any way due to the presence of a normal copy of this gene on the second X chromosome. In men, the second chromosome is Y, so in this case the disease develops.
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Probability of heredity Each person is a carrier of several pathological genes. When both father and mother carry a mutation in the same gene, there is a 25% chance that a child will inherit it from both parents. The probability that one of the parents will pass on a gene with a mutation, and the other - a normal one is 50%, and then a healthy carrier of the disease, the same as each of the parents, will be born. It is also possible that both parents will pass genes without mutation to the child, its probability is 25%.
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Such diseases include hemophilia, cystic fibrosis, phenylketonuria, retinoblastoma, Down syndrome, ataxia, etc.
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Hemophilia Hemophilia is a hereditary disease characterized by a violation of the blood coagulation mechanism. Hemophilia occurs due to genetic disorders; in half of all cases, the disease is familial.
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In 80% of cases, hemophilia is due to the absence or insufficiency of biologically active factor VIII, antihemophilic globulin, in the blood plasma. As a result, blood clotting time is prolonged and patients suffer from severe bleeding even after minimal trauma.
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Historical reference. Certain ethnic groups, in which consanguineous marriages are traditionally frequent, are characterized by their own monogenic diseases. If the mother and father are close relatives, there is a high risk that they both have damage to the same gene. This was typical for many royal and royal families. Russia was no exception.
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The last of the Romanov dynasty - Tsarevich Alexei suffered from hemophilia, which was proved by scientists who conducted a study of the remains of the royal family found near Yekaterinburg. DNA analysis revealed traces of hemophilia. Many descendants of Queen Victoria suffered from the disease. It should be noted that the successor Russian throne Tsarevich Alexei was her great-great-grandson.
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Biology teacher, Talozhenskaya secondary school Utkina Yu.V.
Lesson topic: Human hereditary diseases, their causes and prevention
Talozhnya 2012
human hereditary diseases
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Hereditary diseases: Monogenic diseases Chromosomal diseases Polygenic diseases Risk factors for the occurrence of hereditary diseases Prevention and treatment of hereditary diseases
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Verification work
Option 1 Option 2 1. How many autosomes are in 1. How many human sex chromogenotypes? catfish in the human genotype? 2. What is the sex of a person 2. What is the sex of a person homogametic? heterogametic? 3. Where is located in a person? catfish at the father? 4. To whom are genes transferred, 4. Where are they located on the Y-chromosome in humans? female hemophilia gene? 5. What is the genotype of a boy with 5. What is the genotype of a girl with hemophilia? with color blindness?
Write down the question numbers, against them the correct answers
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The portrait of Leopold I depicts the family signs of the Habsburgs - a protruding lower lip and a protruding chin.
albinism
Hemophilia Queen Victoria and Tsarevich Alexei
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Hereditary diseases are human diseases caused by chromosomal and gene mutations. The terms “hereditary disease” and “congenital disease” are often mistakenly used as synonyms, however, congenital diseases are those diseases that are already present at the birth of a child and can be caused by both hereditary and exogenous factors during pregnancy.
Mutations are sudden, persistent changes in genes and chromosomes that are inherited.
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Mutations Causes of hereditary diseases
Somatic In somatic cells
Generative In germ cells
Monogenic Chromosomal Polygenic
Mitochondrial
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Slide 8
If a mutation occurs in a cell at the early stages of ontogenesis, tissues will develop from it, all cells of which will carry this mutation. The earlier a somatic mutation occurs, the larger is the area of the body that carries the mutant trait.
In humans, somatic mutations often lead to malignant tumors. Breast cancer is the result of somatic mutations
1. Somatic mutations
Slide 9
2. Generative mutations 2. 1. Monogenic - mutations in one gene
The general frequency of gene diseases in the population is 1-2% Caused by mutations or the absence of individual genes and are inherited in full accordance with Mendel's laws Clinical manifestations arise as a result of the absence of certain genetic information, or the implementation of defective.
Albinism
Slide 10
2.1.1 Autosomal dominant monogenic diseases
The action of the mutant gene is almost always manifested. Sick boys and girls are born with the same frequency. The probability of developing the disease in the offspring is 50%. It is based on a violation of the synthesis of structural proteins or proteins that perform specific functions (for example, hemoglobin)
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Disease Examples
Morfan's syndrome Achondrioplasmia Albright's syndrome Claw syndrome Thalassemia (formation of fetal hemoglobin), etc.
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A hereditary connective tissue disease caused by multiple gene mutations, manifested by skeletal changes: tall with a relatively short body, long spider-like fingers (arachnodactyly (from the Greek "daktil" - a finger and Arachne - according to the myth - a woman turned into a spider by Athena), looseness of the joints, often scoliosis, deformities of the chest (fossa or keel), arcuate The eyes are also affected.
Morfan's syndrome
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Famous people with Marfan syndrome
Akhenaten N. Paganini
C. de Gaulle A. Lincoln
Hans Christian Andersen
Slide 14
Another example of the reverse of the previous disease is Achondrioplasmia. Low growth, in an adult 120-130cm. a large skull with a protruding occiput, a sunken bridge of the nose, shortened limbs. The intelligence of such people is normal.
The type of inheritance is autosomal dominant, 80% of cases are due to new mutations.
Reproduction of a painting by the famous painter Diego Valassnes (1599-1660).
Achondrioplasmia
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A strange tribe of ostrich people (Sapadi) in Central Africa is distinguished from other inhabitants of the Earth by an amazing property: they have only two fingers on their feet, and both are big! This is called the claw syndrome. It turned out that the first and fifth fingers were strongly developed on the foot, the second, third and fourth were completely absent. This feature is fixed in the genes of the tribe and is inherited. Sapadis are excellent runners, they climb trees like monkeys, jumping from one tree to another.
By the way, the gene that generates this syndrome is dominant, it is enough for one of the parents to have it, and the child will be born with deformity.
claw syndrome
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2.1.2 Autosomal recessive monogenic diseases
The mutant gene appears only in the homozygous state, and the heterozygous state is the so-called "carrier" Sick boys and girls are born with the same frequency. The probability of having a sick child is 25%. Parents of sick children may be phenotypically healthy, but are heterozygous carriers of the mutant gene. Autosomal recessive inheritance is more typical for diseases in which the function of one or more enzymes is impaired, the so-called fermentopathy
Slide 17
Phenylketonuria Microcephaly Ichthyosis (not sex-linked) Progeria Albinism Sickle cell anemia Cystic fibrosis
Slide 18
Damage to a gene on chromosome 12. Accompanied by the accumulation of phenylalanine and its toxic products, which leads to severe damage to the central nervous system, which manifests itself, in particular, in the form of mental retardation. With timely diagnosis, pathological changes can be completely avoided if, from birth to puberty, the intake of phenylalanine with food is limited.
Phenylketonuria
The main thing is a strict diet! Late initiation of treatment, although it gives a certain effect, does not eliminate the previously developed irreversible changes in brain tissue.
Slide 19
sickle cell anemia
Red blood cells that carry hemoglobin S instead of normal hemoglobin A under a microscope have a characteristic crescent shape (sickle shape), for which this form of hemoglobinopathy is called sickle cell anemia. RBCs that carry hemoglobin S
have reduced resistance and reduced oxygen-transporting ability
Slide 20
Ichthyosis (Greek - fish) is a hereditary dermatosis, characterized by a violation of keratinization, manifested by the formation of fish-like scales on the skin.
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Progeria
Progeria (Greek progērōs prematurely aged) is a pathological condition characterized by a complex of changes in the skin and internal organs caused by premature aging of the body
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cystic fibrosis
A disease that affects the exocrine glands. The reason is a mutation (deletion of three nucleotides), leading to the absence of phenylalanine. It is inherited in an autosomal recessive manner.
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2.2 Monogenic sex-linked diseases
Duchenne muscular dystrophy, hemophilia A and B, Lesch-Nyhan syndrome, Gunter's disease, Fabry disease (recessive inheritance linked to the X chromosome), phosphate diabetes (dominant inheritance linked to the X chromosome)
Slide 25
Hemophilia
Hemophilia is a hereditary disease characterized by a decrease or impaired synthesis of blood coagulation factors. Usually men suffer from the disease, while women act as carriers of hemophilia. The most famous carrier of hemophilia in history was the English Queen Victoria, who passed on the defective genes to two daughters and her son Leopold, and later to her grandchildren and great-grandchildren, including the Russian Tsarevich Alexei Nikolayevich, whose mother, Tsaritsa Alexandra Feodorovna, was a carrier of the hemophilia gene.
Queen Victoria
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Solve the problem
A woman carrying the hemophilia gene marries a healthy man. What is the probability of having sick children in this family? The incoagulability gene is inherited as an X-linked recessive trait. Only men get sick, and women are carriers.
Slide 27
3. Chromosomal diseases
Occur due to a change in the number or structure of chromosomes. Each disease has a typical karyotype and phenotype (for example, Down syndrome - trisomy 21, karyotype 47). Chromosomal diseases are much more common than monogenic ones and account for 12% of all mutations.
Slide 28
Shereshevsky-Turner syndrome (lack of X in women - XO) Down's syndrome (trisomy 21-XXX) Klinefelter's syndrome (extra X in men - XXY) "Cat's cry" syndrome (loss of a fragment of the fifth chromosome) Patau syndrome (trisomy 13-XXX)
Slide 29
Shereshevsky-Turner syndrome
chromosomal disease, accompanied by characteristic anomalies of physical development, short stature and sexual infantilism. In a child with this disease, instead of the ovaries, strands of connective tissue are formed, the uterus is underdeveloped. Very often, the syndrome is combined with the underdevelopment of other organs. Already at birth, the girl is found to have a thickening of the skin folds on the back of her head, a typical swelling of the hands and feet. Often a child is born small, with low body weight. Monosomy on the sex chromosome - (genotype X0, gender - female). Population frequency 1:3000 newborns.
slide 30
Down syndrome
A disease caused by an anomaly of the chromosome set (trisomy of 21 pairs of autosomes), the main manifestations of which are mental retardation, a peculiar appearance of the patient and congenital malformations
A transverse fold is often found on the palm
Frequency 1 in 700 newborns.
Slide 31
A world of equal opportunity
Down syndrome is not a tragedy if you are loved!
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Loss of a fragment of chromosome 5. With this syndrome, a characteristic crying of a child is observed, resembling a cat's meow, the cause of which is a change in the larynx. The frequency of the syndrome is approximately 1:45000. Sex ratio M1:W1.3.
crying cat syndrome
web-local.rudn.ru Patau syndrome
Polyhydramnios is a characteristic complication of pregnancy when carrying a fetus with Patau syndrome: it occurs in almost 50% of cases. With Patau's syndrome (trisomy 13), severe congenital malformations are observed.
Slide 33
Diseases are caused by the polymeric nature of the interaction of genes or a combination of the interaction of several genes and environmental factors (multifactorial diseases). Polygenic diseases are not inherited according to the laws of Mendel. Special tables are used to assess genetic risk.
5. Polygenic diseases (multifactorial)
certain malignant neoplasms, malformations, as well as a predisposition to coronary artery disease, diabetes mellitus and alcoholism, cleft lip and palate, congenital hip dislocation, schizophrenia, congenital heart defects
slide 34
There are 37 genes in mitochondrial DNA, they are involved in energy production, therefore, diseases associated with mutations in mitochondrial genes cause energy deficiency in cells.
At conception, the embryo receives its mitochondria from the maternal egg (paternal ones die).
6. Mitochondrial mutations
Slide 35
Analyze the text on the slide. How can these data be explained? What is the reason?
In 1986, 2,000 hereditary diseases were known, and in 1992 their number increased to 5,000. Every year in Russia, 200,000 children are born with hereditary diseases. Of these, 40,000 remain living with congenital defects. Every year, 90 thousand mentally retarded children and 150 thousand of those who will find it difficult to study are born in the world. Almost every five years, a catalog of human hereditary diseases is published in the world. And every time the list grows. What is it connected with?
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Risk factors (Factors that cause human genetic abnormalities (mutagens)
Physical factors (various types of ionizing radiation, ultraviolet radiation, electromagnetic radiation) Chemical factors (insecticides, herbicides, drugs, alcohol, certain drugs, and other substances) Biological factors (pox, rubella, chicken pox, mumps, influenza, measles, hepatitis. A woman's age is over 35 years, related marriages, the presence of genetic diseases in the family).
Slide 37
In 1986, an international congress of geneticists took place in West Berlin. Based on the materials of the congress, the book "Genetics in Art" was published. It includes photographs and reproductions of sculptures and paintings, which reflect various hereditary pathologies. The models for these works were people suffering from hereditary diseases. These works were created in different historical eras, for example: - Raphael Santi "Sistine Madonna" (XVI century); - Diego Velazquez "Las Meninas" and "Portrait of Sebastian Morro" (VII.v) - Mikhail Vrubel "Portrait of a son" (XIX century)
Slide 38
Sebastian de Morra sitting on the floor
Mikhail Vrubel. Portrait of a son
Raphael Santi "Sistine Madonna" (detail)
Slide 39
In Japan, according to existing legislation, the father, giving his daughter in marriage, must allocate a plot of land to the young family. So that the land does not go to strangers, brides and grooms are often selected among relatives. In such families, there is a sharp increase in the frequency of hereditary diseases. Explain what it is about? The study of human heredity is difficult. Why? Can hereditary diseases be prevented?
Slide 40
Ways to prevent hereditary diseases
Prohibition on closely related marriages Prohibition on the use of alcohol, drugs, smoking Struggle for cleanliness environment, especially against mutagens Medical genetic counseling Prenatal diagnosis of hereditary diseases
Slide 41
Diet therapy Replacement therapy Removal of toxic metabolic products Influence on the synthesis of enzymes Exclusion of certain drugs (barbiturates, sulfonamides, etc.) Surgical treatment Today, a new method is being actively developed - gene therapy. With this method, defective genes can be replaced with "healthy" ones and the disease can be terminated by eliminating the cause (defective gene).
Gene therapy
Slide 42
Eugenics is the science of human hereditary health and possible methods of actively influencing its evolution
The goal of eugenics is the improvement of human nature.
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1. What diseases are called hereditary? 2. What is the classification of human hereditary diseases? 3. If an unusual chromosomal rearrangement is found in a parent, how might this affect the child? 4. Can chromosomal diseases be cured? 5. What methods of prevention of chromosomal diseases can you offer?
Slide 46
Information sources
Biology. General biology. A basic level of. Textbook 11 cells. I. N. Ponomareva Site www.wikipedia.ru 3. Clinical genetics. Bochkov N.P. M: Medicine 1997 4. Genetics Totsky V.M. Odessa Agroprint 2002 5. Human Genetics Shevchenko V.A. M: VLADOS, 6. Biology lessons 10-11. Expanded planning. 2002A.V. Pimenov 7. Open Internet encyclopedia Wikipedia "Chromosomal diseases", "Gene diseases" 8. The Romanovs. History of the dynasty. Pchelov E.V., - M., Olma-Press, 2003
- hereditary
- human disease
- Yekaterinburg, 2007
- Hereditary diseases:
- Classification
- Monogenic diseases
- Chromosomal diseases
- Polygenic diseases
- Risk factors for hereditary diseases
- Prevention and treatment of hereditary diseases
- Lesson Plan
- Hereditary diseases are human diseases caused by chromosomal and gene mutations.
- The terms “hereditary disease” and “congenital disease” are often mistakenly used as synonyms, however, congenital diseases are those diseases that are already present at the birth of a child and can be caused by both hereditary and exogenous factors.
- hereditary diseases
- Classification
- hereditary diseases
- MONOGENIC
- CHROMOSOMAL
- POLYGENIC
- HEREDITARY DISEASES
- autosomal dominant
- Autosomal recessive
- floor-linked
- genomic mutations
- chromosomal mutations
- They are caused by mutations or the absence of individual genes and are inherited in full accordance with Mendel's laws (autosomal or X-linked inheritance, dominant or recessive).
- Mutations can capture either one or both alleles.
- Monogenic diseases
- Clinical manifestations arise as a result of the absence of certain genetic information or the implementation of a defective one.
- Although the prevalence of monogenic diseases is low, they do not completely disappear.
- For monogenic diseases, "silent" genes are characteristic, the action of which is manifested under the influence of the environment.
- Monogenic diseases
- It is based on a violation of the synthesis of structural proteins or proteins that perform specific functions (for example, hemoglobin)
- The action of the mutant gene is almost always manifested
- The probability of developing the disease in the offspring is 50%.
- autosomal dominant
- disease
- Marfan syndrome
- Albright's disease
- dysostoses
- otosclerosis
- paroxysmal myoplegia
- thalassemia, etc.
- Disease Examples
- http://medarticle37.moslek.ru/articles/15184.htm
- Syndrome of Marfan
- Hereditary connective tissue disease, manifested by skeletal changes: tall with a relatively short torso, long spider-like fingers (arachnodactyly), loose joints, often scoliosis, kyphosis, chest deformities, arched palate. Eye damage is also common. Due to anomalies of the cardiovascular system, the average life expectancy is reduced.
- The high release of adrenaline, characteristic of the disease, contributes not only to the development of cardiovascular complications, but also to the appearance in some individuals of special fortitude and mental endowment. Methods of treatment are unknown. It is believed that Paganini, Andersen, Chukovsky were ill with it.
- Arachnodactyly
- http://www.nld.by/imagebase/ib298/ib_stat14_1.htm
- The mutant gene appears only in the homozygous state.
- Sick boys and girls are born with the same frequency.
- The probability of having a sick child is 25%.
- Parents of sick children may be phenotypically healthy, but are heterozygous carriers of the mutant gene
- The autosomal recessive type of inheritance is more characteristic of diseases in which the function of one or more enzymes is impaired, the so-called fermentopathy
- Autosomal recessive
- disease
- Phenylketonuria
- Microcephaly
- Ichthyosis (not sex-linked)
- Progeria
- Disease Examples
- Progeria (Greek progērōs prematurely aged) is a pathological condition characterized by a complex of changes in the skin and internal organs caused by premature aging of the body. The main forms are children's progeria (Hutchinson (Hudchinson) - Gilford syndrome) and adult progeria (Werner's syndrome).
- Progeria
- Progeria
- I started to get old, life is so short. For many people, it is like a river - Rushing somewhere in the alluring distance, Giving either joy, or sorrow, or sadness.
- Mine is like a rock with a waterfall That falls from the sky like a silver hail; That drop, which is given a second, Only to break on the rocks at the bottom.
- But there is no envy for the mighty river, Which flows smoothly along the path on the sand. Their fate is one, - having finished their wanderings, Find peace in the seas of compassion.
- Let my age be short, I'm not afraid of fate, After all, turning into steam, I'll return to heaven again.
- September 29, 2000
- Bychkov Alexander
- http://images.yandex.ru/yandpage?&q=1900511643&p=0&ag=ih&text=%E8%F5%F2%E8%EE%E7%20%ED%E5%20%F1%F6%E5%EF%EB%E5%ED%ED%FB%E9%20%F1%20%EF%EE%EB%EE%EC&rpt=simage
- Ichthyosis (Greek - fish) is a hereditary dermatosis, characterized by a diffuse violation of keratinization by the type of hyperkeratosis, manifested by the formation of scales on the skin) resembling fish.
- Ichthyosis
- Duchenne muscular dystrophy, hemophilia A and B, Lesch-Nyhan syndrome, Gunter's disease, Fabry disease (recessive inheritance linked to the X chromosome)
- phosphate-diabetes (dominant inheritance linked to the X chromosome)
- disease,
- floor-linked
- A. Occur due to a change in the number or structure of chromosomes.
- b. Each disease has a typical karyotype and phenotype (for example, Down's syndrome).
- V. Chromosomal diseases are much more common than monogenic ones (6-10 out of 1000 newborns).
- Chromosomal diseases
- Shereshevsky-Turner syndrome, Down's disease (trisomy 21), Klinefelter's syndrome (47,XXY), "cat's cry" syndrome
- Genomic mutations
- A disease caused by an anomaly of the chromosome set (a change in the number or structure of autosomes), the main manifestations of which are mental retardation, a peculiar appearance of the patient and congenital malformations. One of the most common chromosomal diseases, occurs on average with a frequency of 1 in 700 newborns.
- Disease
- Down
- A transverse fold is often found on the palm
- Disease
- Down
- Patient's karyotype
- They are caused by the interaction of certain combinations of alleles of different loci and exogenous factors.
- Polygenic diseases are not inherited according to the laws of Mendel.
- Special tables are used to assess genetic risk.
- Polygenic diseases
- (multifactorial)
- certain malignant neoplasms, malformations, as well as a predisposition to coronary artery disease, diabetes mellitus and alcoholism, cleft lip and palate, congenital hip dislocation, schizophrenia, congenital heart defects
- Disease Examples
- Cleft lip and palate account for 86.9% of all congenital malformations of the face
- Cleft lip and palate
- Physical factors (various types of ionizing radiation, ultraviolet radiation)
- Chemical factors (insecticides, herbicides, drugs, alcohol, certain drugs and other substances)
- Biological factors (viruses of smallpox, chickenpox, mumps, influenza, measles, hepatitis, etc.)
- Risk factors
- Medical genetic counseling during pregnancy at the age of 35 years and older, the presence of hereditary diseases in the pedigree
- Exclusion of consanguineous marriages
- Prevention
- diet therapy
- Replacement therapy
- Removal of toxic metabolic products
- Mediametor effect (on enzyme synthesis)
- Exclusion of certain drugs (barbiturates, sulfonamides, etc.)
- Surgery
- Treatment
- http://www.volgograd.ru/theme/medic/stomatology/detskaya_stomatology/23256.pub
- http://images.yandex.ru/yandpage?&q=1900511643&p=0&ag=ih&text=%E8%F5%F2%E8%EE%E7%20%ED%E5%20%F1%F6%E5%EF%EB%E5%ED%ED%FB%E9%20%F1%20%EF%EE%EB%EE%EC&rpt=simage
- http://medarticle37.moslek.ru/articles/15184.htm
- ttp://www.nld.by/imagebase/ib298/ib_stat14_1.htm
- http://l.foto.radikal.ru/0612/08e0016d1d34.jpg
- Scientific.ru
- www/volgograd.ru
- Information sources
Relevance of the topic
Due to the increase in the background of ionizing
radiation and environmental pollution
mutagens, the number of hereditary
human changes are increasing.
WHO registers annually 3-4 new
hereditary anomalies. That's why
knowledge in the field of medical genetics is of no small importance, the main
whose task is to identify and
prevention of hereditary diseases.
Human hereditary diseases
arise as a result of violations in the hereditary (genetic) apparatus of germ cells of both or one of the parents.
The working classification of human hereditary diseases includes:
- diseases caused by a single gene mutation (monogenic or Mendelian diseases);
- syndromes caused by chromosomal abnormalities
(chromosomal diseases);
- multifactorial diseases as a result
interactions of genetic and environmental factors (diseases with hereditary predisposition).
hereditary pathology
monogenic diseases, caused by gene mutations
Chromosomal diseases
determined by chromosomal and genomic mutations
Diseases with hereditary predisposition
(multifactorial)-
due to the total (additive) effect of several gene mutations, each of which alone cannot cause the development of the disease. A prerequisite for the occurrence of such diseases is the impact of adverse environmental factors.
Fermentopathies (enzymopathies)
Pathology
autosome
Dysplasia – disruption of tissue structure
Pathology of the genital
chromosomes
Syndromes of multiple congenital malformations – different tissues and systems are involved
Monogenic diseases -
diseases based on a single gene mutation that leads to a change in the order of nucleotides in DNA, which affects the amino acid sequence in the protein.
The main symptom indicating the monogenic nature of the pathology is
is the Mendelian nature of inheritance.
Before mutation After mutation
Enzyme
sign
RNA Enzyme
Gene (DNA)
sign
T - A
C - G
C - G
G - C
T - A
T - A
C - G
G - C
G - C
A - T
G - C
T - A
Gene (DNA)
T - A
C - G
G - C
T - A
T - A
C - G
G - C
G - C
A - T
G - C
T - A
dropping out
Diseases of amino acid metabolism -
Phenylketonuria (PKU) - a disease caused by a defect in the enzyme phenylalanine hydroxylase, resulting in the process of converting phenylalanine to tyrosine is disrupted.
PKU is inherited in an A-P pattern.
Frequency 1:10,000 newborns.
As a result of an enzyme defect, the amino acid
phenylalanine is not absorbed by the body.
Unabsorbed phenylalanine is converted to
phenylpyruvic acid.
Being in the blood in high concentration,
have a toxic effect on the nerve
brain cells.
As a result: dementia, epileptic
seizures, dysregulation
motor functions.
Patients have poor pigmentation due to
melanin synthesis disorders.
A A X A A
carriers
AA A A A A aa
sick
Phenylketonuria (PKU)
The diagnosis of PKU is made by a simple biochemical test.
(Felling's test) or Guthrie's microbiological test.
Treatment is diet therapy. The diet excludes meat, fish, dairy
products and other products containing animal and, in part,
vegetable protein.
Assign amino acid mixtures devoid of phenylalanine
Phenylalanine Tyrosine
Violation of carbohydrate metabolism
Galactosemia
- Type of inheritance A-R. Frequency 1:50000.
- The disease is characterized by damage to the central nervous system, impaired liver function, as a result of a deficiency of the enzyme galactose-1-phosphate-uridyltransferase.
- The disease occurs when breastfeeding as a result of intolerance to milk sugar (lactose), which breaks down in the intestine to galactose.
- An excessive amount of products of incomplete breakdown of lactose accumulates in the tissues, causing clinical manifestations of galactosemia in a child: vomiting, diarrhea, body weight decreases, jaundice develops, etc.
Subsequently, cataracts cirrhosis of the liver, mental retardation.
- The diagnosis of galactosemia is based on the detection of galactose in the urine.
- Treatment is the exclusion of milk sugar from food.
cataract
cirrhosis
liver
in the urine
galactose
Hereditary defects in lipid metabolism
Sphingolipidoses are diseases of the intracellular accumulation of sphingolipids caused by a defect in the enzymes that catalyze their breakdown.
Sphingolipids are structural components of cell membranes, in particular the myelin sheaths of nerve fibers.
Warren Tey-
British ophthalmologist
Tay-Sachs disease
- A-P type of inheritance. Frequency 1:50000
- Clinical picture: lesion of c.n.s. (spinal cord and brain).
- Intelligence is reduced to the point of idiocy.
- Movement disorders leading to complete immobility.
- There is a decrease in vision, subsequent - atrophy of the visual
nerves and blindness.
- Death occurs at 3-4 years of age.
Bernard Sachs
– American neuropathologist
15 chromosome gene mutation
Diseases of steroid metabolism
Adrenogenital syndrome
- A-P type of inheritance.
Frequency 1:5000-1:67000.
- Clinical picture: in girls, the disease manifests itself in the form of pseudohermaphroditism, and in boys - premature virilization.
- The syndrome is caused by dysfunction of the adrenal cortex (excessive secretion of androgens). The body produces an excess of sex hormones and glucocorticoids.
- Large amounts of androgenic 17-ketosteroids are found in the urine.
- The initial sex is determined by the sex chromatin in the cells of the buccal epithelium.
Diseases of the blood coagulation system
Hemophilia A– X-linked recessive type of inheritance. It is caused by a defect in blood coagulation factor 8 (antihemophilic globulin).
Clinical picture: hemorrhages predominate
in large joints of the extremities, subcutaneous and intramuscular hematomas, the presence of blood in the urine.
Hemophilia B– X-linked recessive type of inheritance. Due to a defect in factor 9 (the plasma component of thromboplastin). Clinical manifestations as in hemophilia A. Occurs 10 times less frequently.
Hemophilia C- autosomal dominant, due to a sharp change in antihemophilic globulin (factor 8) and a decrease in the activity of the factor necessary to maintain the integrity of the vessel walls. There is a moderate bleeding tendency.
Dysplasia
Marfan syndrome -
hereditary pathology of connective tissue.
HELL type of inheritance; frequency 1: 20000;
The synthesis of collagen and elastin is impaired due to damage to the gene on chromosome 15, which is responsible for for the synthesis of fibrillin (connective protein
tissue, which forms its elasticity).
- Characteristic appearance of patients:
Pathology of the musculoskeletal system : long and thin limbs with the same fingers, kyphoscoliosis, hyperextension in the joints.
visual impairment (subluxation of the lens, myopia).
Cardiovascular disorders systems: valvular heart disease and aortic aneurysm.
Human chromosomal diseases caused by changes in structure
and the number of autosomes and sex chromosomes
Less than 1% of newborns are born with chromosomal diseases.
Deviations in the number of sex chromosomes and autosomes are associated with the process of meiosis disruption. Most anomalies are incompatible with life.
The final diagnosis of chromosomal diseases is established by the cytogenetic method.
The risk of having a child with a chromosomal abnormality increases with the age of the mother.
The process of meiosis
I division
meiosis
I division
meiosis
normal meiosis
II division of meiosis
II division of meiosis
zerosomy
fertilization
fertilization
Zygote - trisomy
(2n + 1)
Zygote - trisomy
(2n + 1)
Zygote is monosomy
(2n - 1)
1n 1n 1n 1n
Changes in the number of chromosomes cause disturbances in their distribution among daughter cells during meiotic divisions I and II in gametogenesis or in the first divisions of a fertilized egg.
Syndrome "cat's cry"
- Karyotype 46,XX or XY, 5P- (deletion of the short arm
fifth chromosome).
- Frequency 1:45000
- Characteristic: microcephaly, mental retardation;
- low birth weight and muscular hypotension;
- moon-shaped face with wide-set eyes;
- auricles are deformed and low located;
- characteristic crying of a child, reminiscent of a cat
meowing, as a result of underdevelopment of the larynx.
- Most patients die in the first years
about 10% of patients reach 10 years of age.
Jerome Lejeune -
French scientist
Chromosome 5
deletion rate
Patau Syndrome
- Karyotype 2n = 47, XX+13 – trisomy 13; Frequency 1:10000
- This syndrome is represented by two variants: trisomy
And translocation form: 46, XX, -13, -15, + t (q13q15); Clinical signs:
- severe microcephaly,
- anomalies of the eyeball (microphthalmia and anophthalmos),
- cleft lip and palate,
- polydactyly,
- congenital malformations of internal organs,
- Early mortality, dies within a year
- 90% of children. 5% live up to 3 years.
Claus Patau
Trisomy 13 chromosomes
Edwards syndrome
Karyotype 2n=47(+18). Trisomy 18 Frequency 1:6500
Clinical signs:
- protruding occiput, underdevelopment of the lower jaw,
- deformed and low-lying ears,
- anomalies of the limbs, syndactyly.
Pathology of internal organs:
- heart defects, hydronephrosis, cryptorchidism.
Characterized by severe mental retardation.
30% die in 1 month,
less than 10% survive to a year.
John Edwards
Trisomy 18 chromosomes
Down's disease
Karyotype 2n = 47(+21). Trisomy 21.
A translocation option is also possible:
karyotype 46 chromosomes, 14, +t (14.21);
Frequency 1:500 - 1:1000
The frequency of birth of such children depends on the age of the mother.
John Langdon Down (1828-1896) English physician
Translocation form -14,+t(14.21)
Trisomy 21
1 2 3 4 5 6 7 8 9
- 2 3 4 5 6 7 8 9
10 11 12 13 14 15 16 17 18
10 11 12 13 14 15 16 17 18
19 20 21 22 xy or xx
19 20 21 22 x y x x
Down's disease
Clinical signs:
small round head with oblique occiput, Mongoloid incision of the eyes, epicanthus, short nose with a wide flat bridge of nose,
small deformed ears, half-open mouth with protruding language, dementia. S.S.S. defects are observed.
Dermatoglyphic features:
"monkey fold" - deep transverse furrow (40% of cases),
the only flexion crease on the little finger (20-25% of cases), crease of the big toe.
- 20-30% die before the year, 50% - in the first five years, 3% live to
50 years.
epicanthus
Clinodactyly of the 5th finger (curved little finger) - 60%
Shereshevsky-Turner syndrome
- Karyotype 2n = 45 (XO). Monosomy X0. The phenotype is female.
- The frequency of occurrence is 1:2500.
- The main pathological sign in this syndrome is underdevelopment
ovaries (rudimentary strands, consisting of connective tissue.
- Disproportion of the body is characteristic: the upper part is more developed (broad shoulders and narrow pelvis), the lower limbs are shortened.
- Growth is always below the average (135-145 cm).
- Short neck with folds of skin extending from the back of the head ("sphinx neck") .
underdevelopment
ovaries
XX XO
Shereshevsky-Turner syndrome
Norm
Shereshevsky-Turner syndrome
- Express diagnostics is carried out cytological method V
somatic cells: sex chromatin in the cells of such
women are missing.
- Patients are infertile, because. ovaries are not developed.
- The introduction of sex hormones during puberty,
contributes to the development of secondary sexual characteristics.
X- chromatin
In women - the norm: 46 (XX)
X- chromatin is absent
In women - Shereshevsky-Turner syndrome: 45 (XO)
Klinefelter syndrome
- Karyotype 2n = 47(XXY). The male phenotype. Frequency 1:1000
- Clinical signs:
underdevelopment of the testes, lack of spermatogenesis.
- This develops the eunuchoid body type:
narrow shoulders, wide pelvis, female-type fat deposition, poorly developed muscles, sparse vegetation on face or complete absence. The patients are infertile.
- Extra chromosome - X causes a variety of
mental disorders, mental retardation.
- The diagnosis is made by determining in the scraping of the mucosa
shells of the buccal body of sex chromatin.
Harry Klinefelter
x x y x y
Klinefelter syndrome
Norm
Other variants of sex chromosome polysomy
- 47.XXX- trisomy-X.
Frequency 1:1000. Most women have a number of unsharp
deviations in physical development, dysfunction
ovaries, premature menopause, slight
decline in intelligence. Often infertile, 30% of such patients
preserve the generative function.
- 48.XXXX- severe mental retardation.
- 47,XYY- with an increase in the number of Y chromosomes, the sex glands
developed normally, growth is usually high, there are
some dental anomalies. However, significant delays
mental development are rare.
- 48, XXYY, 48,XXXY, 49,XXXYY, 49,XXXXY - other options
Klinefelter syndrome. There are deeper
violations of physical and mental development.
Anomalies of karyotypes in hereditary diseases
Change in the hereditary apparatus
Karyotype
Disease
Monosomy on the X chromosome, including mosaicism
Shereshevsky-Turner syndrome
Klinefelter syndrome
X chromosome polysomy in men
47,XXY; 48,XXXY;
47,XX, 13+; 47,XY, 13+
Trisomy on the 13th chromosome
Patau Syndrome
Edwards syndrome
47,XX, 18+; 47,XY, 18+
Trisomy on the 18th chromosome
47,XX, 21+; 47,XY, 21+
Down syndrome
Trisomy on the 21st chromosome
Short arm deletion
5th chromosome
crying cat syndrome
46,XX, 5p-; 46, xy, 5p-
Short arm deletion
15 chromosomes
Prader-Willi syndrome
46 XX or XY, 15r-.
Multifactorial diseases
Set of genes
- These are the most common diseases:
rheumatism, congenital heart disease,
hypertension and peptic ulcer disease,
cirrhosis of the liver, diabetes, psoriasis,
bronchial asthma, schizophrenia, etc.
- The likelihood of getting sick is determined
- degree of hereditary
predisposition and
- by the influence of environmental factors
Disease
Set of environmental factors
Treatment of hereditary diseases
- Gene therapy -
elimination of genetic
defect by introducing
genes into patient cells
directed
gene changes
defects or giving
cells of new functions
(for example, treatment
congenital
immunodeficiency in 1990
year with the help
gene transplants.
- Warning
diseases in offspring
(when genes are transferred to
sex cells).
- pathogenetic
(substitute,
corrective) and
symptomatic
therapy - normalization
violations without direct
impact on the main
genetic defect:
- diet therapy
with the exception of receipt
with the food of those substances
whose concentration in
increased blood
(for example, treatment of PKU
diet.)
- replacement therapy
(hormones, enzymes, etc.)
For example, the introduction
factor VIII in hemophilia)
- surgical correction
congenital defects, etc.
Treatment of hereditary diseases with HT
A bacterium carrying a plasmid
cloned normal ADA gene
Genetically deactivated retrovirus
Gene therapy scheme for severe combined immunodeficiency (SCID) caused by defective adenosine deaminase (ADA) gene
T-lymphocytes isolated from a patient
Cloned ADA gene is introduced into the virus
A retrovirus infects blood cells by transferring ADA genes into them.
Genetically modified cells are reimplanted and produce ADA
Cells are grown in culture to ensure that the ADA gene is active