Genetic diseases that are inherited. Medical genetic examination

Diseases with a hereditary predisposition are diagnosed quite often. The hereditary predisposition to disease is increased risk its occurrence in a child of a sick mother or father. In other words, if a mother or father suffers from any disease, it can be transmitted to their born child, and the development of pathologies that are characterized by a hereditary predisposition occurs when exposed to external factors.

The basis of hereditary predisposition is the genetic uniqueness of the organism, which manifests itself in its individual reaction to external factors.

Types of diseases with hereditary predisposition

There is a hereditary predisposition to certain diseases:

1. Monogenic.

One mutant gene is included in the basis of monogenic diseases. Development occurs under the influence of a specific external factor. These include the body's reaction to drugs, dust, food additives, weather conditions.

2. Polygenic.

Polygenic diseases with a hereditary predisposition have a basis with several genes that are normal rather than altered. Their mutation is observed under the same influence of factors external environment. Almost 90% of all chronic diseases are polygenic diseases. non-infectious nature. These include ischemic disease, diabetes mellitus, peptic ulcer disease.

Let us consider in more detail which diseases have a hereditary predisposition.

cystinuria

Cystinuria can be attributed to hereditary diseases.

Cystinuria is common congenital anomaly. The cause is a mutation in the Slc3a1 gene. For a child to develop a disease, it is enough to inherit one mutated gene from each parent.

In other words, the disease is caused by the occurrence of stones in the kidney (kidneys). At the same time, a person has renal colic and more rarely renal failure. The risk zone for the disease of this organ includes children (from 10 years old) and adults up to 30 years old. You may also experience symptoms such as abdominal pain, arterial hypertension.

The treatment of such a disease in a child and an adult is primarily aimed at reducing the concentration of cystine so that there is no further education stones in the bladder and kidneys. Yes, recommended plentiful drink, which will help dissolve the cystine.

Cystine dissolves well in an acidic environment. To achieve the required pH of urine, special preparations are prescribed. But it is worth noting that such drugs increase the risk of such a component in the urine and kidneys as an alkaline stone.

If conservative treatment fails, resort to surgical intervention. At acute syndrome kidney failure kidney transplant is recommended.

flat feet

Is flat feet hereditary? There is a myth that flat feet is a hereditary disease, and if one of the parents had it, then future children will definitely inherit it. This is not so, because only a predisposition to the disease can be transmitted. The development of flat feet can occur under the influence of many factors: wearing the wrong shoes when the foot begins to deform, systematic stress on the feet, etc. But it can also be prevented by following some rules, which we will consider below.

Symptoms of flat feet may include:

rapid fatigue of the feet;
puffiness that occurs at the end of the day;
muscle cramps;
posture deformity;
quick wear of shoes on the inside of the foot.

Treatment consists in carrying out massage, medical - physical culture complex. In this case, orthopedic insoles are useful, the type of which is determined by the doctor, based on the course of the disease and its type.

Plantar (plantar fasciitis)

These diseases include plantar (plantar) fasciitis. Basically, plantar fasciitis, or, in other words, a heel spur, is an acquired disease. But there is also an innate conditioning factor, which is weakness. connective tissue, which significantly increases the risk of overloading the ligaments of the foot.

With the disease, there is a sharp pain in the heel area, which is observed when stepping on the foot. In the first stages of the course of the disease, pain only worries in the morning, when a person gets out of bed and takes the first steps. During the day, the pain goes away and comes back after prolonged immobility limbs. There may also be a difference in leg length, but not significant.

With the help of an x-ray, a bony growth on the heel can be seen, which should be removed as soon as possible. Treatment, first of all, consists in unloading the feet: elimination excess weight, flat feet, limitation of physical activity. In this case, insoles are simply irreplaceable and with the same effect.

If there is a strong pain syndrome, painkillers are prescribed. To reduce inflammation, non-steroidal drugs are effective. Also prescribe physiotherapy, which contribute to pain relief and inflammation.

Scoliosis

The disease is in the formation physiological bend spine in a pathological direction to the side. In this case, rotation of the bodies of the spine and the progression of the disease with a change in the age and growth of the child are observed.

There are cervical, cervico-thoracic, thoracic, lumbar-thoracic and lumbar scoliosis. Symptoms are as follows: spinal deformity, asymmetric position of the folds on the buttocks and legs, impaired functioning internal organs, flat feet, the difference in the length of the limbs (one limb is shorter than the second).

To eliminate such a symptom as different leg lengths, orthopedic insoles and insoles are used. But in any case, different leg lengths are corrected only when the underlying disease, scoliosis, is cured. So, to correct different lengths of the legs and eliminate other symptoms, physiotherapy, massage and exercise therapy are carried out.

syndactyly

The next type of this kind of disease is syndactyly. The genetically determined disease syndactyly is an abnormal development of the fingers, or rather, their fusion. The cause of the occurrence is a violation of the separation of the fingers during the period embryonic development fetus.

The tendency to such deformation of the fingers of the fetus is observed in those women who have experienced harmful effects, including x-rays, as well as infection of the body during pregnancy.

The symptoms of the disease are clearly pronounced: non-separation of the fingers, the difference in their length and thickness, which can lead to the child's tightness and depression. Treatment, as a rule, is surgical, during which the fused fingers are separated. After the operation, the fingers can exist and function separately from each other.

Ischemia

Ischemic heart disease is a dysfunction of the organ, which is the result of insufficient oxygen supply to the heart muscle through coronary arteries. A common cause is atherosclerosis of the arteries.

Symptoms of the disease can be called: arrhythmia, weakness, nausea, shortness of breath, increased sweating, pain syndrome in the heart area with irradiation to nearby areas, human mental disorders (panic fear, anxiety, melancholy).

The treatment of the disease is to eliminate the pain syndrome special preparations, taking other medicines prescribed by the doctor, good rest.

There is a tendency in children to such a hereditary disease as diabetes mellitus. This ailment is endocrine disease, which occurs as a result of the absence or insufficient secretion of the hormone insulin in the body or with its indigestibility by internal organs. Factors that give impetus to the development of the disease are:

overweight;
the presence of pathology of the pancreas;
disturbed metabolism;
maintaining an inactive lifestyle;

stress;
alcohol;
the course of pathologies in the body that reduce immunity;
the use of drugs that have a diabetic effect.
Symptoms of a disease with a hereditary predisposition are as follows:
frequent trips to the toilet;
constant thirst, which leads to dehydration;
weight loss;
weakness and fatigue;
violation of the visual system;
feeling of numbness of the limbs;
heaviness in the legs;

dizziness;
low body temperature;
the occurrence of cramps in the calf muscles;
itchy skin syndrome in the perineum;
heartache.

A common symptom is a violation of the functioning of the liver, which occurs regardless of the type of disease. This is due to an increase in blood glucose levels. At untimely treatment disease occurs in the death of liver cells, which are replaced by connective tissue. In this case, cirrhosis of the liver occurs.

Typically, diabetes is incurable disease, but by maintaining normal blood sugar levels, complications can be prevented or reduced. For this, a diet is prescribed, which consists in limiting the consumption of sugar-containing foods, as well as foods with the presence of fats and cholesterol. It is equally important to observe moderate loads.

Also, the doctor prescribes hypoglycemic drugs that are taken every day.

Hereditary diseases can also be attributed to such as a stomach ulcer. But this is not always inherited. So, only 40% of parents with this disease will have children with an ulcer. Disease-causing factors include:

Drugs that a person takes for a long time. These include Aspirin, Diclofenac and other non-steroidal anti-inflammatory drugs. AT old age there is a risk of getting sick when taking such drugs with coagulants and glucocorticoids.
The presence of tuberculosis, syphilis, diabetes mellitus, lung cancer, liver cirrhosis, pancreatitis in the body increases the risk of ulcers.
Injury to the abdomen (strike, bruise, burn, frostbite).
Exposure to the bacterium Helicobacter pylori, which can be contracted through a kiss, dirty hands, common utensils, as well as from mother to fetus.

The symptoms of a stomach ulcer are as follows:

Syndrome of pain in the abdomen. The pain is usually mild in intensity, but in some cases it can be severe. Increased pain is observed with the use of alcohol, spicy and smoked foods, with physical exertion.
The occurrence of heartburn (burning in the epigastric region), which occurs in almost 80% of people suffering from such a disease. Heartburn is a process when the acidic contents of the stomach enter the lumen of the esophagus. The occurrence of such a symptom is observed 2 hours after eating.
Decreased appetite.
The occurrence of nausea. In some cases, nausea is also accompanied by vomiting, which is a consequence of impaired gastric motility.
Heaviness in the stomach after eating.
The appearance of an eructation.

Treatment of stomach ulcers, first of all, consists in maintaining proper nutrition. So, the use of spicy, hot and coarse food, as well as alcohol is unacceptable.

Treatment with medicines consists in taking antibiotics, antacids, gastroprotectors, reparants. In the event that the ulcer is multiple or recurrent, as well as if complications arise, an operation is prescribed. The operation consists in resection of the stomach and vagotomy - cutting the nerves that stimulate the secretion of acids in the stomach.

In any case, a genetically determined disease can be avoided by following some rules that will help achieve this.

Light-perceiving structures of the eye.

The retina of the eye consists of several layers, its thickness is 0.1-0.2 mm.

The outer layer is pigment cells containing the pigment fuscin; it absorbs light and prevents its scattering; in strong light, the grains of pigment cells move and obscure the rods and cones from bright light.

Then comes a layer of rods and cones, they are visual receptors - photoreceptors. Retinal photoreceptors contain light-sensitive substances: rods - rhodopsin, or visual purple (red), cones - iodopsin (violet).

In bright light, the restoration of rhodopsin does not keep pace with its decay, and cones become light-perceiving receptors at the base. Thus, the rods are the apparatus of twilight vision, and the cones are daytime.

Conductor department of the visual analyzer.

When examining the back wall of the eyeball (i.e., the fundus) with a specially concave ophthalmoscope mirror, you can see the area from which the blood vessels diverge and the optic nerve exits. This is the area from which the blood vessels diverge and the optic nerve exits. This area is called the blind spot because it does not contain the rod-and-cone neuroepithelium. Approximately in the center of the retina is the fovea - this is the place of the best vision. It contains only cones.

Plot around fossa painted in yellow and called yellow spot.

The fibers of the optic nerve, extending from the retina, cross on the basal surface of the brain.

The muscular apparatus of the eye.

It is essential for normal vision.

The eye is constantly in motion as a result of contraction of the muscles of the eyeball.

Eye muscles:

set the eye for the best vision.

help determine direction

estimate the distance and size of an object

In bright light, the pupil constricts as a result of the contraction of the circular muscles, and less light rays enter the retina. In the dark, the pupil expands due to the contraction of the radial muscles. This process is the adaptation of the eye to the intensity of the light.

Protective apparatus of the eye.

In mammals, the eye is protected by eyelids:

Top reflex close

Lower when irritated

Rudeminated third cornea

Along the edges of the eyelids are glands that secrete eye lubricant, which, when blinking, spreads over the eyeball and protects it from drying out and prevents tears from rolling over the edge of the eyelid.

Lacrimal apparatus:

lacrimal glands of the upper and 3rd eyelids

lacrimal ducts

lacrimal sac

tear duct

The glands secrete tears that moisturize and cleanse the conjunctiva and cornea of the eye. Tears contain lysozyme (a bactericidal substance).

The cornea, lens, vitreous body do not have blood vessels, therefore, the cells of these tissues also receive nutrients from intraocular fluid filling the anterior and posterior chambers of the eye. There are many blood vessels in the iris and ciliary body and nutrients from the blood pass into the chambers of the eye. But only those substances that are part of the aqueous humor penetrate through the walls of the vessels, and its composition differs from the composition of the blood.

This property of the walls of the blood vessels of the eye - to pass some and delay others is called hematoophthalmic, or eye, barrier.

Topic 18. PHYSIOLOGY OF ADAPTATION

Adaptation is the adaptation of organisms to life through properties that ensure their survival and reproduction in a changing environment.

According to ecological and geneticclassification subdivided:

specific (inherited) individual (purchased)

Adaptation criteria are the reactions of the cardiovascular and respiratory systems, blood picture, gastrointestinal function, state of water metabolism, body temperature.

adaptation mechanisms.

In the process of adaptation, the animal organism reacts as a whole with the participation of all its organs and systems, with the central nervous system playing the leading role. Installed exclusively importance in body adaptation sympathetic nervous system.

In the development of the general adaptation of the organism, it is of great importance pituitary-adrenal system. The totality of body reactions in response to the excitation of this system is called adaptation syndrome, or stress.

FROM stage of stress

Alarm reaction Resistance stage Exhaustion stage

The first stage of the "alarm reaction" is characterized by the activation of the adrenal glands and the release of catecholamines and glucocorticoids into the blood.

The second stage is the "stage of resistance" - the body's resistance to a number of extreme stimuli increases.

The third stage, the stage of exhaustion, occurs when the action of stress continues.

Adaptation of animals in industrial complexes.

The crowded placement of animals does not provide the physiologically necessary for them motor activity. Hypodynamia and a high level of abnormal feeding create conditions for cows to become obese, which serves as a predisposing factor in the development of ketosis, lethargy and other pathologies, which indicates incomplete physiological adaptation.

Control tests.

Test on the topic number 1 "Blood system"

Write the terms based on the definitions of the relevant concepts:

The main transport system of the body, consisting of plasma and suspended in it shaped elements.

The liquid part of the blood that remains after the removal of formed elements from it.

Physiological mechanism for the formation of a blood clot.

Non-nuclear blood cells containing hemoglobin.

Formed elements of blood that have a nucleus and do not contain hemoglobin.

The body's ability to defend itself against foreign bodies and substances.

Blood plasma devoid of fibrinogen.

The phenomenon of absorption and digestion of microbes and other foreign bodies by leukocytes.

A preparation of ready-made antibodies formed in the blood of an animal that was previously specially infected with this pathogen.

Weakened culture of microbes introduced into the body of animals.

RBC destruction and release of hemoglobin.

A hereditary disease that is expressed in a tendency to bleed as a result of non-clotting.

A hereditary factor (antigen) found in red blood cells. It was first discovered in macaques.

An animal that receives part of the blood in a transfusion, other tissues or organs in a transplant.

An animal that provides part of its blood for transfusion, other tissues or organs for transplantation into a patient.

A translucent, slightly yellowish alkaline liquid that fills the lymphatic vessels.

The process of formation, development and maturation of blood cells.

0.9% NaCl solution.

The percentage of different types of leukocytes.

Increases during pregnancy infectious diseases, inflammatory processes.

An ancestral cell capable of developing into various types of mature cells.

on topic No. 1 "The blood system"

What is the internal environment of the body?

A. Intercellular fluid

B. Plasma

B. Serum

2. What is the liquid part of the blood?

A. Intercellular fluid

B. Plasma

B. Serum

3. What has the property of attaching and giving off oxygen?

A. Salt

B. fibrin

B. Hemoglobin

G. Fibrinogen

D. Antibodies

E. Calcium salts

G. Leukocytes

4. What blood components form the body's immune system?

A. Red blood cells

B. Platelets

B. Fibrin

G. Fibrinogen

D. Leukocytes

E. Hemoglobin

G. Antibodies

5. What is involved in blood clotting?

A. Red blood cells

B. Platelets

B. Fibrin

G. Fibrinogen

D. Leukocytes

E. Hemoglobin

G. Antibodies

6. What structural features are characteristic of leukocytes, and what functions do they perform?

A. No core

D. There is a core

D. Flat round shape

E. They transport oxygen

G. Destroy bacteria

7. What structural features are characteristic of erythrocytes and what functions do they perform?

A. No core

B. Move amoeba, change shape

D. There is a core

D. Flat round shape

E. They transport oxygen

G. Destroy bacteria

8. What cells and substances transport oxygen?

A. Plasma

B. Platelets

B. Leukocytes

G. fibrin

D. Red blood cells

E. Fibrinogen

J. Hemoglobin

9. What cells are characterized by phagocytosis?

A. Plasma

B. Platelets

B. Leukocytes

G. fibrin

D. Red blood cells

E. Fibrinogen

J. Hemoglobin

10. How can you explain that large cattle not sick with Sap?

A. Natural innate species immunity

B. Natural acquired immunity

B. Artificial immunity

D. There are platelets

D. There are red blood cells

11. What organs are hematopoietic?

A. Red bone marrow in cancellous bone

B. Yellow bone marrow in the cavities tubular bones

B. Liver

D. Lymph glands

D. Heart

E. Stomach

G. Spleen

12. What are the functions internal environment organism?

A. Humoral regulation

B. Motor

B. Nervous regulation

G. Transport

D. Protective

E. Cell nutrition

Scheme on topic No. 2 "Immune system"

Describe the immune system according to the basic scheme.

And mmmunity

Congenital Acquired

(non-specific protective factors) (specific protective factors)

- skin - immune system response

- mucous membranes

- inflammation of the lymphocytes

- phagocytosis (neutrophils

monocytes) B-cells T-cells

cell antibodies

humoral cellular

Erlich discovered

acquired immunity

Natural Artificial

passive active passive active

(immunity (after illness)

newborn) vaccine

serum colostral (weakened

(ready-made antibodies) (with colostrum from mother) microbes or their poisons)

Leukocytes

Nonspecific Specific (thymus

Spleen

lymph nodes

Red bone

Phagocytes Lymphocytes

identifiers

(devourers)

T cells B cells

T-helpers (helpers)

Cellular T-suppressors (suppress)

Immunity T-killers (killers)

interferon humoral Plasma cells Memory cells

Immunity

Lysozyme Antibodies

Testing knowledge on topic No. 3 "The system of blood and lymph circulation"

What is a cardiac cycle? What phases does it consist of?

Explain the terms diastole and systole.

Why does blood move in the same direction in the heart?

Why is the heart able to work continuously throughout life?

What is automatism of the heart?

How does the strength and frequency of heart contractions change during exercise?

In what state are the valves of the heart during the contraction of the atria, ventricles, during a pause?

How does the nervous system control the heart?

What is the importance of an abundant blood supply to the heart muscle?

The walls of the right ventricle are thinner than the left. How can this be explained?

The contraction of which parts of the heart (atria or ventricles) lasts longer? What can explain their unequal duration of work?

What is the conduction system of the heart, and what is its role in the automatism of the heart?

Does the same amount of blood pass through the left and right sides of the heart? Why can't this number be different?

The experience of the German physicist Goltz is known when he caused a cardiac arrest with a sharp blow to the belly of a frog. How to explain this fact?

In the proposed list of statements, select the correct ones and write down the numbers under which they are written.

Every cell in the body needs nutrients, oxygen, and water to survive.

In organisms with open circulatory system cells are bathed directly in blood.

In organisms with an open circulatory system, blood pressure is usually high and blood flows rapidly.

Lymph is a colorless liquid formed from blood plasma by filtering it into the intercellular space and from there into the lymphatic system.

Functions of circulating blood: transport, regulatory, protective.

The heart muscle cannot stimulate the contraction of the heart.

The cardiac muscle has a structure identical to the skeletal muscles.

The thickness of the walls of the atria and ventricles is the same throughout the heart.

The atria are the lower chambers of the heart that receive blood returning from the pulmonary circulation.

The largest blood vessel is the aorta.

Heart contractions are regulated only with the help of impulses that occur in the heart itself.

The lymphatic system is a collection of nodes, vessels and lymphoid tissue.

Systolic pressure is the blood pressure when the ventricles relax.

Aneurysm is an expansion of the lumen of the arteries due to protrusion of its wall.

Hypertension is low blood pressure.

The maximum speed of blood movement is created in the aorta and arteries.

Pulse is a rhythmic fluctuation of the walls of the veins that have arisen due to changes in pressure in the vessels in the rhythm of the contraction of the heart.

Adrenaline is a hormone that dilates blood vessels.

Chemoreceptors - receptors that perceive blood pressure in the walls of the aorta and carotid arteries.

The movement of blood in the veins is provided low pressure, activity skeletal muscle and the presence of pocket valves.

The arterial pulse of cattle at rest averages 60-80 beats per minute.

Physiological dictation.

Arteries are the vessels that carry blood. . .

Veins are called vessels that carry blood. . .

Arrange the blood vessels in order of decreasing blood flow. ..

Arrange the blood vessels in order of decreasing pressure in them. . .

What type of muscle tissue makes up the heart muscle?

Blood pressure at the time of contraction of the ventricles is called. . .

Blood pressure during relaxation of the ventricles is called. . .

Blood pressure readings are expressed in two numbers: the smaller one shows ... .. pressure, the larger one -. . .

The rhythmic contraction of the walls of the arteries with each systole of the left ventricle is called. . .

A wave of increased pressure, accompanied by an acceleration of blood flow and expansion of the arterial walls, is called ... ..

The main function of the heart valves. . .

Determine the location:

A) tricuspid valve (....);

B) double-leaf (....);

B) semilunar valves (...).

13. Name the two main vessels that transport blood from the heart (....).

14. Name the arteries that transport blood to the lungs (....).

15. Why does the left ventricle have a thicker muscular wall? (……).

16. Name the types of blood vessels ....

17. Name the layers that form the walls of the artery (...)

18. What layer of the walls of arteries prevents their damage? …

19. What is the function of the middle layer of arterial walls? (...).

20. What type of blood vessel has a wall consisting of a single layer of endothelial cells? …

21. Blood returns to the heart through the veins at low pressure. What feature of the structure of the veins ensures the movement of blood through them? (...).

22. Name the arteries that supply blood to the heart muscle. (….).

23. What chamber of the heart does the aorta depart from? (…..).

24. What is the cardiac cycle? (….).

25. The cardiac cycle consists of:

26. What part nervous system regulates the duration of the heart? (...).

27. Name the specialized structures of the heart that cause rhythmic contractions and act as conducting systems:

28. Define the pulse.

29. What is the cause of the pulse?

On the test questions

studies disciplines"Culturology" directed on the formation next competencies: ... professional spheres. Given educational allowance will allow students think deeper theoretical... For example, anatomy, pathology and physiology maybe one...

Today, gynecologists advise all women to plan their pregnancy. After all, in this way many hereditary diseases can be avoided. This is possible with a thorough medical examination of both spouses. There are two points in the question of hereditary diseases. The first is a genetic predisposition to certain diseases, which manifests itself already with the maturation of the child. So, for example, diabetes mellitus, which one of the parents suffers from, can manifest itself in children in adolescence, and hypertension - after 30 years. The second point is directly genetic diseases with which the child is born. They will be discussed today.

The most common genetic diseases in children: description

The most common hereditary disease of a baby is Down syndrome. It occurs in 1 case out of 700. A neonatologist makes a diagnosis in a child while the newborn is in the hospital. In Down's disease, the children's karyotype contains 47 chromosomes, that is, an extra chromosome is the cause of the disease. You should know that girls and boys are equally susceptible to this chromosomal pathology. Visually, these are children with a specific facial expression, lagging behind in mental development.

Shereshevsky-Turner disease is more common in girls. And the symptoms of the disease appear at the age of 10-12: patients are short in stature, the hair on the back of the head is low set, and at 13-14 they do not have puberty and no menses. In these children, there is a slight lag mental development. The leading sign of this hereditary disease in adult woman is infertility. The karyotype for this disease is 45 chromosomes, that is, one chromosome is missing. The prevalence of Shereshevsky-Turner disease is 1 case per 3000. And among girls up to 145 centimeters tall, it is 73 cases per 1000.

Only males have Klinefelter's disease. This diagnosis is established at the age of 16-18 years. Signs of the disease - high growth (190 centimeters and even higher), slight mental retardation, disproportionately long arms. The karyotype in this case is 47 chromosomes. A characteristic sign for an adult male is infertility. Kleinfelter's disease occurs in 1 in 18,000 cases.

Manifestations are enough known disease- hemophilia - usually observed in boys after one year of life. Mostly representatives of the strong half of humanity suffer from pathology. Their mothers are only carriers of the mutation. Blood clotting disorder is the main symptom of hemophilia. Often this leads to the development of severe joint damage, such as hemorrhagic arthritis. With hemophilia, as a result of any injury with a cut in the skin, bleeding begins, which for a man can be fatal.

Another hard one hereditary disease- cystic fibrosis. Usually, children under one and a half years old need to be diagnosed to identify this disease. Its symptoms are chronic inflammation of the lungs with dyspeptic symptoms in the form of diarrhea, followed by constipation with nausea. The frequency of the disease is 1 case per 2500.

Rare hereditary diseases in children

There are also genetic diseases that many of us have not heard of. One of them appears at the age of 5 years and is called Duchenne muscular dystrophy.

The carrier of the mutation is the mother. The main symptom of the disease is the replacement of skeletal striated muscles with connective tissue that is incapable of contraction. In the future, such a child will face complete immobility and death in the second decade of life. Not for today effective therapy Duchenne muscular dystrophy, despite many years of research and the use of genetic engineering.

Another rare genetic disease is osteogenesis imperfecta. This is a genetic pathology of the musculoskeletal system, which is characterized by deformation of the bones. Osteogenesis is characterized by a decrease in bone mass and their increased fragility. There is an assumption that the cause of this pathology lies in congenital disorder collagen metabolism.

Progeria is a fairly rare genetic defect that is expressed in premature aging organism. There are 52 cases of progeria in the world. Up to six months, children are no different from their peers. Further, their skin begins to wrinkle. Manifested in the body senile symptoms. Children with progeria usually do not live beyond the age of 15. The disease is caused by gene mutations.

Ichthyosis is a hereditary skin disease that occurs as a dermatosis. Ichthyosis is characterized by a violation of keratinization and is manifested by scales on the skin. The cause of ichthyosis is also a gene mutation. The disease occurs in one case in several tens of thousands.

Cystinosis is a disease that can turn a person into stone. The human body accumulates too much cystine (an amino acid). This substance turns into crystals, causing hardening of all body cells. The man gradually turns into a statue. Usually such patients do not live up to 16 years. The peculiarity of the disease is that the brain remains intact.

Cataplexy is a disease that has strange symptoms. At the slightest stress, nervousness, nervous tension all the muscles of the body suddenly relax - and the person loses consciousness. All his experiences end in fainting.

Another strange and rare disease is extrapyramidal system syndrome. The second name of the disease is the dance of St. Vitus. Her attacks overtake a person suddenly: his limbs and facial muscles twitch. Developing, the syndrome of the extrapyramidal system causes changes in the psyche, weakens the mind. This disease is incurable.

Acromegaly has another name - gigantism. The disease is characterized by a high growth of a person. And sickness is caused overproduction somatotropin growth hormone. The patient always suffers from headaches, drowsiness. Acromegaly today also has no effective treatment.

All these genetic diseases are difficult to treat, and more often they are completely incurable.

How to identify a genetic disease in a child

The level of today's medicine makes it possible to prevent genetic pathologies. To do this, pregnant women are encouraged to undergo a set of studies to determine heredity and possible risks. In simple words, genetic analyzes are done to identify the propensity of the unborn baby to hereditary diseases. Unfortunately, statistics show an increasing number genetic abnormalities in newborns. And practice shows that most genetic diseases can be avoided by curing them before pregnancy or by terminating a pathological pregnancy.

Doctors emphasize that for future parents, the ideal option is to analyze for genetic diseases at the stage of pregnancy planning.

Thus, the risk of transmitting hereditary disorders to the unborn baby is assessed. For this, a couple planning a pregnancy is advised to consult a geneticist. Only the DNA of future parents allows us to assess the risks of having children with genetic diseases. In this way, the health of the unborn child as a whole is also predicted.

The undoubted advantage of genetic analysis is that it can even prevent miscarriage. But, unfortunately, according to statistics, women resort to genetic analyzes most often after a miscarriage.

What influences the birth of unhealthy children

So, genetic analyzes allow us to assess the risks of having unhealthy children. That is, a geneticist can state that the risk of having a baby with Down syndrome, for example, is 50 to 50. What factors affect the health of the unborn child? Here they are:

The age of the parents. With age, genetic cells accumulate more and more “breakdowns”. This means that the older the father and mother, the higher the risk of having a baby with Down syndrome.
Close relationship of parents. Both cousins and second cousins more likely are carriers of the same diseased genes.
The birth of sick children to parents or direct relatives increases the chances of having another baby with genetic diseases.
Chronic diseases of a family nature. If both father and mother suffer, for example, from multiple sclerosis, then the probability of the disease and the unborn baby is very high.
Parents belonging to certain ethnic groups. For example, Gaucher's disease, manifested by damage to the bone marrow and dementia, is more common among Ashkenazi Jews, Wilson's disease - among the peoples of the Mediterranean.
Unfavorable environment. If future parents live near a chemical plant, a nuclear power plant, a cosmodrome, then polluted water and air contribute to gene mutations in children.
Exposure to radiation on one of the parents is also an increased risk of gene mutations.

So, today, future parents have every chance and opportunity to avoid the birth of sick children. Responsible attitude to pregnancy, its planning will allow you to fully feel the joy of motherhood and fatherhood.

Especially for - Diana Rudenko

Along with diseases, clearly determined by heredity (genes and chromosomes) or environmental factors (injuries, burns), a large and diverse group of diseases, the development of which is due to the interaction of certain hereditary influences (mutations or combinations of alleles) and the environment. This group of diseases is called diseases with hereditary predisposition.

The causes and features of the development of these diseases are very complex, multilevel, not fully elucidated and different for each disease. However, it is generally accepted that there are common features in the development of such diseases.

The basis of hereditary predisposition to diseases is a wide genetically balanced polymorphism of human populations with enzymes, structural and transport proteins, as well as antigenic systems. In human populations, at least 25-30% of the loci (out of about 40,000) are represented by two or more alleles. So, individual combinations of alleles are incredibly diverse. They provide the genetic uniqueness of each person, expressed not only in abilities, physical differences, but also in the body's reactions to pathogenic environmental factors. Diseases with a hereditary predisposition occur in individuals with the corresponding genotype (a combination of "attractive" alleles) in the case of provoking environmental influences.

Diseases with a hereditary predisposition are conditionally divided into the following main groups: congenital malformations; mental and nervous diseases are common; diseases of middle age are common.

The most common birth defects development is splitting upper lip and palate, hip dislocation, clubfoot, etc. To mental and nervous diseases with hereditary predisposition include schizophrenia, epilepsy, manic-depressive circular psychoses, multiple sclerosis and others. Among the somatic diseases of middle age, psoriasis, bronchial asthma, stomach and duodenal ulcers often occur, ischemic disease heart disease, hypertension, diabetes mellitus, etc.

In connection with the success of deciphering the human genome, new scientific achievements have expanded the possibilities of genetic analysis of the mechanisms of the occurrence of diseases with a hereditary predisposition, despite their complexity. The pathogenesis of such a disease is a complex, multifaceted and multilevel process, so the significance of hereditary factors cannot be unambiguously determined in all cases. It is often difficult to separate the factors from each other both in terms of intensity and duration of their action. Understanding the causes and course of diseases with a hereditary predisposition is further complicated by the fact that their development is the result of interaction genetic factors(monogenic or polygenic) with environmental factors very specific or less specific. Only the latest achievements in the study of the genome and the compilation of gene maps of human chromosomes make it possible to approach the identification of the effects of the main abnormal gene.

Each disease with a hereditary predisposition is a genetically heterogeneous group with the same clinical end-points. Within each group there are several varieties due to genetic and non-genetic causes. For example, the group of coronary heart diseases can be divided into several monogenic forms of hypercholesterolemia (high blood cholesterol).

The reasons for the development of diseases with a hereditary predisposition are schematically shown in Fig. 5.19. their quantitative combinations in the development of diseases may be different in different people.

For the manifestation of diseases with a hereditary predisposition, a specific combination of hereditary and external factors is necessary. The more pronounced the hereditary predisposition and the larger the bodies of the environment, the higher the likelihood for the individual to get sick (at an earlier age and in a more severe form).

Rice. 5.19.

The comparative significance of external and hereditary factors in the development of diseases is schematically shown in fig. 5.20.

Rice. 5.20.

Three levels of hereditary predisposition and three degrees of environmental influence are conditionally defined: weak, moderate and strong. With a weak hereditary predisposition and a slight influence of the environment, the body maintains homeostasis and the disease does not develop. However, in case of strengthening harmful factors in a certain part of the faces it will manifest itself. With a significant hereditary predisposition to pathology, the same environmental factors cause malaise in more people.

Diseases with a hereditary predisposition are different from other forms hereditary pathology(genetic and chromosomal) clinical picture. Unlike genes, in which all members of the proband family can be divided into sick and healthy, the clinical picture of a disease with a hereditary predisposition has continuous transitions within the same form of pathology.

Diseases with a hereditary predisposition are characterized by differences in their manifestation and severity depending on gender and age. The mechanisms of the spread of such diseases over time are quite complex, since in populations both genetic characteristics of propensity and environmental factors can change in different directions.

A feature of diseases with a hereditary predisposition is an increased frequency (accumulation) in certain families, due to their genetic constitution. Figure 5.21 shows examples of pedigrees burdened with hypertension (a) and allergic diseases (b). Genealogical analysis of such pedigrees makes it possible to accurately determine the prognosis of the course of pathology in the family, as well as therapeutic and preventive measures against it.

Rice. 5.21.

Hereditary predisposition to the disease can have a monogenic or polygenic basis.

CHAPTER IX. Human hereditary diseases

9.1 The concept, classification and features of hereditary pathology

Pathology is any deviation from the normal course of biological processes - metabolism, growth, development, reproduction.

Hereditary pathology is a deviation from the norm with an established fact of inheritance, that is, transmission from generation to generation. It is necessary to distinguish between a congenital pathology - present from the birth of an individual - from a hereditary pathology. Congenital pathology can be caused by the action of environmental factors - a lack of nutrients and oxygen during fetal development, birth injuries, infections, and so on. The establishment in accordance with the requirements of genetic analysis (Chapter II) of the fact of inheritance of an abnormal trait is the only basis for recognizing the hereditary nature of the pathology.

There are two types of classification of hereditary pathology. The first (accepted mainly in domestic literature) - clinical type. According to this type of classification, there are four groups of diseases:

Group I - these are actually hereditary diseases - chromosomal and gene diseases (Edwards and Patau syndromes, phenylketonuria, cystic fibrosis);

Group II - diseases with a pronounced hereditary predisposition, in the pathogenesis of which the manifestation of hereditary factors is determined by the action of specific external circumstances (arterial hypertension, diabetes mellitus, gout);

Group III- diseases that are determined mainly by environmental factors, but in the pathogenesis of which hereditary factors play a certain role (glaucoma, atherosclerosis, breast cancer);

Group IV - diseases to which heredity at first glance is not related ( food poisoning, fractures, burns).

It should be noted that the frequently used concepts of "familial" and "sporadic" diseases are not directly related to heredity. Family diseases are observed in relatives, but can also be caused by the action of the same external causes, for example, the nature of the diet. Sporadic cases occur in individual individuals, but may also be due to a rare combination of alleles or a de novo mutation.

The second classification system - genetic - is generally accepted in foreign literature and has recently become more and more popular. frequent use and literature in Russian. According to this system, five groups are distinguished:

Group I - gene diseases determined by mutations in certain genes. These are predominantly monogenic traits with autosomal dominant, autosomal recessive, sex-linked dominant, sex-linked recessive, hollandric and mitochondrial inheritance patterns (Chapter II);

Group II - chromosomal diseases, that is, genomic and chromosomal mutations (Chapter V);

Group III - diseases with a hereditary predisposition, in the pathogenesis of which environmental and hereditary factors play a role, having a monogenic or polygenic type of inheritance (myopia, morbid obesity, stomach ulcers).

Group IV - genetic diseases of somatic cells, often associated with malignant neoplasms(retinoblastoma, Wilms tumor, some forms of leukemia);

Group V - diseases of genetic incompatibility between mother and fetus, which develop as a result of the mother's immune response to fetal antigens (incompatibility for the Rh factor and some other antigen-antibody erythrocyte systems).

Hereditary diseases can begin their manifestation in different ages. The nature of the manifestation (the time of manifestation of the first symptoms of the disease) is specific for different forms hereditary pathology. As a rule, hereditary diseases are characterized by a chronic (long-term) progressive (with an increase in the severity of symptoms) course.

9.2 Chromosomal diseases

This group includes diseases caused by abnormalities in the number or structure of chromosomes. About 1% of newborns have an abnormal karyotype, and among stillborns, the incidence of aberrations in the number or structure of chromosomes is 20%. General characteristic features chromosomal diseases are: low weight at birth, developmental delay, short stature, microcephaly, micrognathia, osteogenesis disorders, abnormal eye position. More detailed description chromosomal diseases are given in sections 5.8 and 5.9.

9.3 Genetic diseases

Genetic diseases Pathological conditions caused by gene mutations are called. Most often, this concept is applied to monogenic diseases.

This group is characterized by heterogeneity - the same diseases can be caused by mutations in different genes. The general principles for the development of pathology at the gene level can be:

Production of an abnormal protein product;

Absence of normal protein;

An insufficient amount normal protein;

An excess of a normal protein product.

According to the nature of violations of homeostasis (the constancy of the internal environment of the body), the following groups of gene diseases are distinguished:

1. Diseases of amino acid metabolism.

The largest group of hereditary metabolic diseases. Almost all of them are inherited in an autosomal recessive manner. The cause of diseases is the insufficiency of one or another enzyme responsible for the synthesis of amino acids.

Phenylketonuria- violation of the conversion of phenylalanine to tyrosine due to a sharp decrease in the activity of phenylalanine hydroxylase - an autosomal recessive disease. It appears at the age of 2-4 months, the first symptoms are lethargy, convulsions, eczema, a "mouse" smell (the smell of ketones). Severe brain damage gradually develops, leading to a sharp decrease in intelligence up to idiocy. If from the first days of life completely exclude (or significantly limit the amount) phenylalanine from the diet of a sick child before puberty, symptoms do not develop. The disease is caused by mutations in the gene PAH, which codes for phenylalanine-4-hydroxylase. Gene PAH localized to HSA12q24.1. Several dozen mutations of this gene have been described in different populations. There are diagnostic systems based on PCR that can detect heterozygous carriage. Recently, new approaches to the treatment of phenicetonuria have been developed - replacement therapy with phenylalanine lyase, a plant enzyme that catalyzes the breakdown of phenylalanine into harmless metabolites, and gene therapy by inserting a normal phenylalanine hydroxylase gene into the genome.

Alkaptonuria- autosomal recessive disorder of tyrosine metabolism and accumulation in body tissues ( articular cartilage, tendons) of homogentisic acid. Manifestation takes place in childhood. The first symptom is dark urine. Often develops urolithiasis disease and pyelonephritis. The accumulation of degradation products of homogentisic acid leads to damage to the joints (primarily knee and hip). There is a darkening and increased fragility of the connective tissue. Darkening of the sclera and auricles is characteristic. Mutations in a gene HGD- homogentisic acid oxidases are the cause of this disease. This gene contains 14 exons and is located in HSA3q21-23. About 100 different missense mutations, frameshift type mutations and splice site changes have been described that are associated with this disease. .

Oculocutaneous albinism 1- absence or significant lack of pigment in the skin, hair, iris and pigment membranes of the eye (Figure IX, 1).

Figure IX, 1. The representative of the Negroid race is an albino. Based on materials from the site http://upload.wikimedia.org/wikipediacommons/99a/Albinisitic_man_portrait

A disease with an autosomal recessive mode of inheritance. Manifested in varying degrees depigmentation of the skin, hair, iris and pigment membranes of the eye, decreased visual acuity, photophobia, nystagmus, frequent sunburn. Various missense mutations, frameshift-type mutations, and nonsense mutations in the tyrosinase gene ( TYR, HSA11q24) are responsible for this disease.

2. Disorders of carbohydrate metabolism

Galactosemia- the absence or significant decrease in the activity of the enzyme galactose-1-phosphate-uridyltransferase and the accumulation of galactose and its derivatives in the blood, which have a toxic effect on the central nervous system, liver and lens of the eye. In the first days and weeks of life, jaundice, liver enlargement, nystagmus, muscle hypotonia, and vomiting are observed. Over time, a cataract develops, a lag in physical and mental development. Characterized by intolerance to milk.

The disease has an autosomal recessive mode of inheritance. Several forms of this disease are caused by different mutant alleles of the gene GALT(galactose-1-phosphate uridyltransferase), localized in the region of HSA9p13. Missense mutations reduce the activity of the enzyme to varying degrees, which determines the varying severity of symptoms of the disease. For example, Durte's galactosemia is almost asymptomatic, only a tendency to liver disorders is noted.

Gierke's disease (glycogenosis type I, glycogen disease type I)- the inability to convert glucose-6-phosphate into glucose, which leads to a violation of the synthesis and decomposition of glycogen. Glycogen deposition occurs, the reverse process does not. Hypoglycemia develops. Accumulation of excess glycogen in the liver and kidneys leads to liver and kidney failure. The type of inheritance is autosomal recessive. The cause of the disease is a mutation in the gene G6PC, which codes for the enzyme glucose-6-phosphatase. 14 mutant alleles of this gene have been described and are associated with Gierke's disease. There are molecular genetic tests to detect heterozygous carriage and prenatal diagnosis of this disease.

3. Lipid metabolism disorders

Niemann-Pick disease types A and B- decreased activity of the enzyme acid lysosomal sphingomyelinase, which is encoded by the gene SMPD1(HSA11p15.4-p15.1). The type of inheritance is autosomal recessive. Violation of lipid metabolism leads to the accumulation of lipids in the liver, lungs, spleen, and nervous tissues. Characterized by degeneration of nerve cells, disruption of the nervous system, elevated level cholesterol and lipids in the blood. Type A is lethal in early childhood. Type B is milder, and patients usually survive to adulthood. Different types are caused by different mutations in the gene SMPD1.

Gaucher disease (glycosylceramide lipidosis)- accumulation of glucocerebrosides in the cells of the nervous and reticuloendothelial system, due to a deficiency of the enzyme glucocerebrosidase, which is encoded by the gene GBA(HSA1q21). It belongs to the group of lysosomal storage diseases. Some forms of the disease manifest themselves in severe lesions of the liver, spleen, nervous and bone tissues.

4. Hereditary diseases of purine and pyrimidine metabolism

Lesch-Nychen syndrome - sex-linked recessive disease in which the content of uric acid in all body fluids. The consequence of this is developmental delay, moderate mental retardation, seizures aggressive behavior with self harm. Insufficiency of the enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase due to mutations in the gene HPRT1(HSAXq26-q27.2) underlies this disease. Several mutations in the same gene have been described, resulting in gout(violation of purine metabolism and deposition of uric acid compounds in tissues).

5. Disorders of connective tissue metabolism

Marfan's syndrome ("spider fingers", arachnodactyly)- damage to the connective tissue due to a mutation in the gene FBN1(HSA15q21.1), responsible for the synthesis of fibrillin. It is inherited in an autosomal dominant manner. The clinical polymorphism of the disease is explained a large number mutant alleles, each of which can manifest itself in a heterozygous state. Patients are characterized by high growth, asthenic physique (disproportionately long limbs), arachnodactyly (long thin fingers), weakness ligamentous apparatus, retinal detachment, lens subluxation, prolapse mitral valve(Picture IX, 2).

Figure IX, 2. Marfan syndrome. Based on materials from the site http://www.spineinfo.ru/infosources/case/cases_14.html.

Mucopolysaccharidoses- a group of connective tissue diseases associated with impaired metabolism of acid glycosaminoglycans (mucopolysaccharides) caused by a deficiency of certain lysosomal enzymes. These diseases are referred to as lysosomal storage diseases. They manifest themselves in various defects of bone and connective tissues. Mucopolysazaridosis type I (Hurler's syndrome)- an autosomal recessive disease resulting from a deficiency of the alpha-L-iduronidase enzyme due to mutations in the IDUA gene (HSA4q16.3). This leads to the accumulation of protein-carbohydrate complexes and fats in the cells of the body. As a result, patients have small stature, significant mental retardation, enlarged liver and spleen, heart defects, corneal clouding, bone deformity, and coarsening of facial features (Figure IX, 3).

Figure IX, 3. Hurler syndrome. Adapted from http://medgen.genetics.utah.edu/photographs/pages/hurler_syndrome.htm.

Mucopolysaccharidosis type II(Hunter syndrome) is a sex-linked recessive disorder caused by a defect in the enzyme iduronate sulfatase due to a mutation in the IDS gene (HSAXq28). The accumulation substances are dermatan and heparan sulfates. Characterized by coarse facial features, scaphocephaly, noisy breathing, deep rough voice, frequent acute respiratory viral infections (Figure IX, 4 ) . At the age of 3-4 years, there are violations of coordination of movements - the gait becomes clumsy, children often fall when walking. Patients are characterized by emotional lability and aggressiveness. Progressive hearing loss, nodular skin lesions of the back, osteoarthritis, corneal lesions are also observed.

Figure IX, 4. Hunter Syndrome. Based on materials from the site http://1nsk.ru/news/russia/23335.html.

Mucopolysaccharidosis type III (Sanfilippo syndrome, Sanfilippo disease) - disease caused by the accumulation of heparan sulfate. It is characterized by genetic heterogeneity - there are 4 types of this disease caused by mutations in 4 different genes encoding enzymes involved in the metabolism of the accumulated substance. The first symptoms of the disease in the form of sleep disorders appear in children older than 3 years. Apathy gradually develops, there is a delay in psychomotor development, speech disorders, facial features become rough. Over time, children stop recognizing others. For patients, growth retardation, joint contractures, hypertrichosis, moderate hepatosplenomegaly are typical. Unlike the Hurler and Hunter syndromes, mental retardation predominates in Sanfilippo disease, and corneal lesions and of cardio-vascular system missing.

Figure IX, 5. Sanfilippo Syndrome. Adapted from http://runkle-science.wikispaces.com/Sanfilippo-syndrome.

Fibrodysplasia (myositis ossificans, paraossal heterotopic ossification, Münheimer's disease)- a disease of the connective tissue associated with its progressive ossification as a result of a mutation in the gene ACVR1(HSA2q23-q24), which encodes the activin A receptor. The mode of inheritance is autosomal dominant. The disease manifests itself birth defects development - primarily curved big toes and disorders in cervical region spine at the level of the vertebrae c2 - c7. The disease is progressive in nature, leading to significant impairment functional state of the musculoskeletal system, severe disability of patients and death mainly in childhood and young age (Figure IX, 6). The disease is also called the "disease of the second skeleton", since where regular anti-inflammatory processes should occur in the body, bone growth begins.

Figure IX, 6. Fibrodysplasia. Based on materials from the site http://donbass.ua/news/health/2010/02/15.

6. Circulating protein disorders

Hemoglobinopathies- hereditary disorders of hemoglobin synthesis. There are two groups of hemoglobinopathies. The first is characterized by a change in the primary structure of the globin protein, which may be accompanied by violations of its stability and function (for example, sickle cell anemia). With hemoglobinopathies of the second group, the structure of hemoglobin remains normal, only the rate of synthesis of globin chains is reduced (for example, β -thalassemia).

7. Metabolic disorders in erythrocytes

hereditary spherocytosis- congenital deficiency of erythrocyte envelope lipids. The disease is characterized by an autosomal dominant or autosomal recessive mode of inheritance, depending on the gene mutation SPTA1(HSA1q21), which encodes erythrocyte α-1 spectrin. An anomaly of this protein leads to an increase in the concentration of sodium ions inside the erythrocyte, and the penetration of excess water into it due to an increase in osmotic pressure. As a result, spherical erythrocytes are formed - spherocytes, which, unlike biconcave normal erythrocytes, do not have the ability to change shape in narrow sections of the bloodstream, for example, when passing into the sinuses of the spleen. This leads to a slowdown in the advancement of erythrocytes in the sinuses of the spleen and the splitting off of a part of the erythrocyte membrane with the formation of microspherocytes. The destroyed erythrocytes are taken up by macrophages in the spleen. Hemolysis of erythrocytes leads to hyperplasia of pulp cells and enlargement of the spleen. One of the main clinical symptoms is jaundice. The main symptoms of hereditary spherocytosis are an enlarged spleen (usually protruding from under the hypochondrium by 2-3 cm) and jaundice. Sometimes there are signs of delayed development, disorders facial skeleton, tower skull, saddle nose, high palate, teeth dislocation, narrow eye sockets.

8. Hereditary diseases of metal metabolism

Konovalov-Wilson disease (hepatocerebral dystrophy)- an autosomal recessive disorder of copper metabolism, leading to severe lesions of the central nervous system and internal organs. The disease is caused by low or abnormal synthesis of ceruloplasmin (copper-transporting protein) due to insufficient enzymatic activity of the copper-transporting ATPase. Mutations (about 200 described) in the gene ATP7B(HSA13q14-q21) lead to changes in the β-polypeptide of this enzyme, which is the genetic basis of this pathology. The main role in the pathogenesis is played by a violation of copper metabolism, its accumulation in the nervous, renal, hepatic tissues and cornea, as a result of which toxic damage copper of these organs. Large-nodular or mixed cirrhosis is formed in the liver. In the kidneys, the proximal tubules are the first to be affected. In the brain, the basal ganglia, the dentate nucleus of the cerebellum, and the substantia nigra are affected to a greater extent.

9. Malabsorption in the digestive tract

Cystic fibrosis (cystic fibrosis) - autosomal recessive disease characterized by damage to the glands of external secretion, severe violations respiratory functions and gastrointestinal tract. Caused by mutations in the gene CFTR(HSA7q31.2), which encodes a transmembrane regulator of cystic fibrosis. The disease is characterized by damage to the external secretion glands, severe disorders of the functions of the respiratory system and the gastrointestinal tract.

Lactose intolerance (hypolactasia) - autosomal recessive pathological condition of poor digestion of lactose ( milk sugar), the genetic basis of which are mutations in the regulatory and coding regions of the gene LCT(HSA2q21), which codes for lactase. This enzyme is expressed predominantly in the intestinal ciliary cells and is responsible for the breakdown of lactose into galactose and glucose. The main symptoms of lactase deficiency are flatulence, abdominal pain, diarrhea, and vomiting. In children, lactase deficiency may manifest chronic constipation, restlessness and crying after eating. In different human populations, the frequencies of mutant alleles vary from 1 to 100%.

10. Hormonal disorders

Testicular feminization (Morris syndrome) - a sex-linked recessive disorder in which a female (46,XY) karyotype exhibits a female phenotype. expressiveness varies. With incomplete feminization, the gonads develop in a male pattern, but some sexual characteristics correspond to the female sex with varying degrees of severity - a hypertrophied clitoris, incomplete closure of the scrotal suture, scrotum-shaped labia majora, a shortened vagina (Figure IX, 7). With complete feminization, the main symptom is the absence of menstruation and sexual hair growth with well-developed mammary glands and a female phenotype. The disease is caused by various mutations in the gene AR(HSAXq11-q12), which codes for the androgen receptor.

Figure IX, 7. View of the external genitalia with incomplete testicular feminization. Based on materials from the site http://www.health-ua.org/img/woman/tabl/8_17.jpg.

Androgenital syndrome (female pseudohermaphroditism) - an endocrine disorder with an autosomal recessive type of inheritance, in which the patient has a male-type external genitalia and a female hormonal structure. In patients, the clitoris is enlarged, which becomes similar to a male penis with one urogenital opening, there is no external entrance to the vagina, the labia minora are absent, the large lips look like a "chopped" scrotum. In this case, the internal genital organs may have a normal appearance. The genetic basis of the disease are gene mutations CYP21(HSA6q21.3), which encodes the enzyme 21-hydroxylase of the cytochrome P450 group, which is involved in the synthesis of the hormones aldosterone and cortisol.

9.4 Molecular markers in the study of hereditary pathology

A significant part of hereditary diseases and diseases with a hereditary predisposition are not monogenic in nature. They can be attributed to quantitative traits, that is, those that have a continuous series of variability and can be measured - for example, height, weight, limb length. alleles a large number genes contribute to the manifestation of such traits, therefore they are called polygenic. Tracing their inheritance and identifying genes whose alleles are involved in pathological processes can be done using genetic markers. Identification of linked inheritance (association) phenotypic traits With genetic markers allows you to find regions of chromosomes that provide decisive influence on the processes under study (positional cloning), and to obtain reliable systems for molecular diagnostics (molecular labeling). Currently, the most common markers in human genetics are microsatellite loci (Figure IX, 8; Section 8.1) and mononucleotide polymorphic sites - SNPs (Figure IX, 9), the main features of which are shown in Table IX, 1.

Analysis of gene expression (of all or a group) on biochips in tissues related to a particular hereditary disease, in normal and pathological conditions, often makes it possible to identify candidate genes for the disease under study. Chromosomal localization of DNA sequences affecting a quantitative trait (QTL) can be determined based on co-inheritance with several closely spaced markers. If it is possible to find markers that limit the QTL on both sides, then, based on the genomic sequencing data (Sections 7.7 and 8.4), it is possible to compile a list of genes that are positional candidates for the QTL of the disease under study. With the simultaneous use of expression analysis and the study of disease associations with molecular markers, it is possible to determine the most likely candidate genes - those that appear on both lists.

The degree of susceptibility to certain drugs and the effectiveness of their use varies widely. For the same disease, the appropriate drug for a particular individual is often selected by trial and error. In addition to wasting time, this approach sometimes causes irreparable harm to health. Currently for a large number medicines systems of markers based on SNP have been developed that allow a priori (before experiment) to predict the reaction of an individual organism to a particular chemical substance. Associations of individual allelic variants of DNA markers with the characteristics of biochemical reactions are the basis of individual therapy (Figure IX, 10).

Figure IX, 8. In microsatellite loci, the unit of variability is a group of nucleotides.

Figure IX, 9. In mononucleotide polymorphic sites (SNPs), the unit of variation is one nucleotide.

Table IX, 1. Comparison of the main characteristics of SNPs and microsatellites.

Figure IX, 10. The principle of selecting individual therapy based on mononucleotide repeat polymorphism - SNP.

Control questions and tasks for chapter IX

1. Which group of hereditary diseases can be attributed to cystic fibrosis?

2. Can a heterozygote for a gene mutation SPTA1 to be hereditary spherocytosis?

3. What hereditary disease is caused by the accumulation of heparan sulfate?

4. Why is there four possible SNP alleles?

Additional Reading for Chapter IX

N.P. Bochkov. Clinical genetics // M.: Geotar-Med. 2002. - 457 p.