X and the human chromosome. X and the chromosome. XY sex chromosomes

- Tell me, professor! You said that in 5 million years the Sun will reach such a size that it will swallow the Earth. It's true?
- Not. This will only happen in 5 billion years.
- AND! Well, thank God!

Today the press spread the news that soon “ the world will be left without men", what " the male Y chromosome - and with it the entire male gender - are under threat of extinction", what " men will disappear like dinosaurs», « disappear from the face of the earth», « will disappear as a species". Can you believe these sensations? What is the Y chromosome and what is it for? What is really happening to her? Is there a real threat to the male population? This is what this article is about.

Human hereditary material is organized into 22 pairs of non-sex chromosomes (autosomes) and two sex chromosomes. Half of our chromosomes come from our father and half from our mother. Women have two X chromosomes, while men have one X and one Y chromosome. In fact, the picture is somewhat more complex. About one in five hundred men has two X and one Y chromosomes (XXY), and one in 1000 has one X and two Ys (XYY). Every thousandth woman has three X (XXX).

Having more than two sex chromosomes is not fatal, but can lead to developmental disabilities. In XYY men, the impairments are insignificant: there is a slight deterioration in mental development, increased growth, but at the same time fertility (the ability to leave offspring) is preserved. XXY men are usually infertile, they have less male sex hormone - testosterone, and their genitals are less developed. XXX women are generally fertile, sometimes with developmental delays. Changing the number of copies of autosomes is much more dangerous: three copies of chromosome 21 are the cause of the development of Down syndrome, tripling of any of the other chromosomes is incompatible with life.

It turns out that the gender of people is determined by the presence or absence of the Y chromosome: if there is a Y chromosome, it turns out a man, if it is not there, a woman. This sex determination system is not the only one possible in the animal world. For example, in the fruit fly Drosophila, sex is determined by the number of X chromosomes and does not depend on the presence of a Y chromosome. In birds, unlike humans, two identical sex chromosomes are observed in males, while in females the sex chromosomes are different. The platypus (a unique egg-laying mammal with a beak) has as many as 10 sex chromosomes, which are linked into chains of five: there are XXXXXXXXXXX females and XYXYXYXYXY males. Moreover, one part of the platypus sex chromosome chain has similarities with the sex chromosomes of birds, and the other with the sex chromosomes of other mammals.

In very rare cases, among humans, rodents and some other species of mammals, you can find a male without a Y chromosome, as well as a female with a Y chromosome. It was shown that not the entire Y chromosome is needed to determine sex, but only a small part of it, just one gene. The SRY gene, located on the Y chromosome, is responsible for the development of the testes. If this gene "jumps" to another chromosome, it can turn out to be an XX male. If, as a result of the mutation, the SRY gene is disabled on the Y chromosome, an XY female can be obtained.

In 1991, the scientific journal Nature published the work of molecular biologist Peter Koopman, who managed to insert the SRY gene from the Y chromosome of mice into mouse embryos with two X chromosomes. These transgenic mice were externally males. So it was confirmed that the key genetic difference between a man and a woman lies in a single gene.

But how can one gene affect human development so dramatically? It turned out that the SRY gene can activate other genes responsible for the development of male sexual characteristics. In the female, these genes are turned off, but the appearance of the SRY gene can lead to them being turned on. In other words, every woman's genome contains almost all the necessary instructions for the development of a man, but these instructions are kept locked up. The SRY gene is the key to this lock.

Although Koopman's work showed that one gene was enough to produce XX mice with all the external characteristics of males, the resulting males were sterile. This means that for the full development of the male, one gene is still not enough. Nevertheless, many scientists are inclined to believe that the number of genes important for the development of full-fledged men on the Y chromosome is small.

Recent evidence suggests that the Y chromosome became the sex chromosome approximately 150 million years ago. Then the X and Y chromosomes were very similar, just like modern non-sex chromosomes. Since then, the Y chromosome has steadily decreased in size and lost about 97% of its genes. After becoming a sex chromosome, she began to accumulate genes that were good for men but bad for women, and gradually get rid of everything else.

In addition, the Y chromosome mutates almost 5 times faster than the rest of the chromosomes. It is believed that this is due to the fact that the appearance of male germ cells is preceded by a large number of divisions. The fact is that with each cell division, it is necessary to copy chromosomes so that each new cell gets a full set of genetic material. But the DNA copying system is not ideal: with each copying errors, peculiar typos, mutations occur. The Y chromosome goes through a large number of copies in each generation, because it is inherited only through male germ cells, which means it accumulates more copying errors. Autosomes are inherited from both men and women, which means that in half the generations they are inherited through female germ cells. As a result, they, on average, go through fewer divisions per generation and accumulate fewer mutations.

If you roughly calculate the rate of disappearance of genes from the Y chromosome and the number of genes remaining on it, you can imagine that the Y chromosome will lose all its genes in about ten million years. Today there is a debate about whether the Y chromosome is threatened with complete extinction in the future. First, Koopman's experiments show that the Y chromosome is not so necessary: \u200b\u200bif a couple of genes important for sex determination jump from the Y chromosome to the autosome, we will have a new sex determination system. In such a system, it will be possible to get rid of the Y chromosome without any special consequences. Indeed, in some rodent species, the Y chromosome was completely lost during evolution, which indicates that the scenario described above is indeed possible. Another point of view is that nothing will happen to the Y chromosome. Today, it has been shown that there are a number of evolutionary mechanisms that actively preserve the genes remaining on the Y chromosome. It is not at all necessary that the Y chromosome will continue to lose the genes remaining on it at the same rate with which it lost them before. Despite the existence of different points of view, scientists agree that a decrease in Y will not lead to catastrophic consequences for humanity. The men will stay.

The chromosome is a structural component of the cell nucleus, which contains deoxyribonucleic acid (DNA) - a carrier of hereditary information, as well as protein and some RNA. The set of chromosomes in the nucleus of a somatic cell, both pathological and normal, is called a karyotype. In the human reproductive cell, there are two times less chromosomes - there are 23 of them, that is, the cells are haploid, but upon fertilization, the cell's diploidy is restored. Sex chromosomes can be of two types: X and Y. The female germ cell has two X chromosomes, and the male one has one X and one Y. In all pairs of chromosomes, both sex and autosomal, one of the chromosomes is obtained from the mother, and the other from father. Consequently, the sex of the child depends on which type of male reproductive cell (Y or X) connects to the female (X).

The structure of the chromosome is clearly visible during cell division, when it is highly coiled. The appearance of chromosomes changes significantly at different stages of the cell cycle. The long ends of the chromosome are called telomeres. As a result of an abnormality in the number or structure of human chromosomes, pathological conditions arise, which are called chromosomal syndromes, which cannot be treated. More than three hundred chromosomal abnormalities have been described and studied. Clinical manifestations with chromosome abnormalities are observed from birth.

Sex chromosomes of human karyotype

Human karyotype is a diploid chromosome set of a person, which is a set of morphologically separate chromosomes introduced by parents during fertilization.

The chromosomes of a set are genetically unequal: each chromosome contains a group of different genes. All chromosomes in the human karyotype are divided into autosomes and sex chromosomes. There are 44 autosomes in the human karyotype - 22 pairs of homologous chromosomes and one pair of sex chromosomes - XX in women and XY in men. In terms of shape and size, all homologous autosomes are divided into 7 groups, denoted by Latin letters from A to G. In addition, all homologues in decreasing order of total length are numbered from 1 to 22, and according to the position of the centromere, all chromosomes in the human karyotype are divided into metacentric, submetacentric, acrocentric.

The main indications for the study of human karyotype

Modern methods of karyotyping provide detailed detection of intrachromosomal and interchromosomal rearrangements, violations of the order of chromosome fragments - deletions, duplications, inversions, translocations. Such a study of the karyotype makes it possible to diagnose a number of chromosomal diseases caused by both gross violations of karyotypes (violation of the number of chromosomes) and a violation of the chromosomal structure or a multiplicity of cellular karyotypes in the body. Indications and contingent of persons for chromosome analysis and karyotyping:

Multiple developmental defects,

Persons with identified pathology of sex chromatin,

Severe growth retardation in combination with developmental microanomalies - in a fetus during pregnancy with a high risk of having a child with a chromosomal pathology,

Reproductive dysfunction of unknown origin (infertile marriage, primary amenorrhea, etc.),

Persons with occupational hazards to assess mutagenic effects (chemical, radiation, physical),

Elena Shvedkina about one of the most common genetic diseases - patients complain of infertility, erectile dysfunction, gynecomastia and osteoporosis

Klinefelter's syndrome - a genetic disorder characterized by an additional female sex chromosome X (one or even several) in the male karyotype XY... At the same time, not enough sex hormones are formed in the male gonads - the testes.

As you know, the genetic set of a person has 46 chromosomes, of which 22 pairs are called somatic, and the 23rd pair is sexual. Women have a pair of sex chromosomes XXand men - XY... For Klinefelter's syndrome, the presence of a male Y chromosome is mandatory, therefore, despite additional X-chromosomes, patients are always male.

Classification: types of karyotypes in Klinefelter syndrome

By the number of additional X chromosomes, the following variants of Klinefelter's syndrome are distinguished:

• 47, XXY - the most common
• 48, XXXY
• 49, XXXXY

In addition, male karyotypes are also referred to Klinefelter's syndrome, which include, in addition to additional X-chromosome, additional Y-chromosome - 48, XXYY... And, finally, among patients with this syndrome, there are persons with a mosaic karyotype. 46, XY/47, XXY (that is, some of the cells have a normal chromosome set).

The history of the discovery of the syndrome

The syndrome got its name in honor of Harry Klinefelter, a doctor who, in 1942, first described the clinical picture of the disease. Klinefelter and colleagues published a report on a study of 9 men who shared common symptoms such as poor body hair, eunuchoid body type, tall stature, and reduced testicles. Later, in 1956, geneticists Plankett and Barr (E.R. Plankett, M.L. Barr) found sex chromatin bodies in the nuclei of cells of the oral mucosa in men with Klinefelter syndrome, and in 1959 Polany and Ford (P E. Polanyi, S. E. Ford) with colleagues showed that patients in the chromosome set have an extra X-chromosome.

Active research of this pathology was carried out in the 70s in the USA. Then all newborn boys were subjected to karyotyping, as a result of which it was possible to reliably identify the prevalence and genetic characteristics of Klinefelter's syndrome.

Interestingly, mice can also have sex chromosome XXY trisomy syndrome, which allows them to be effectively used as models for the study of Klinefelter syndrome.

The prevalence of the disease

Klinefelter's syndrome is one of the most common genetic diseases: for every 500 newborn boys, there is 1 child with this pathology.

In addition, Klinefelter's syndrome is the third most common endocrine pathology in men (after diabetes mellitus and thyroid pathology) and the most common cause of congenital reproductive disorders in men.

To date, about half of the cases of Klinefelter syndrome remain unrecognized. Often such patients seek help for infertility, erectile dysfunction, gynecomastia, osteoporosis, anemia, etc. without a previously established diagnosis.

Etiology and causes of violation

Klinefelter's syndrome refers to genetic diseases that are not inherited, since patients, with rare exceptions, are infertile. Pathology, as a rule, occurs as a result of a violation of the divergence of chromosomes in the early stages of the formation of eggs and sperm. At the same time, Klinefelter's syndrome, which occurs due to a violation in the female reproductive cells, occurs three times more often. Mosaic forms are caused by the pathology of cell division in the early stages of embryogenesis; therefore, some of the cells in such patients have a normal karyotype. The reasons for nondisjunction of sex chromosomes and disorders of cell division at the earliest stages of embryogenesis are still poorly understood. Unlike other chromosomal diseases, the influence of the age of the parents is absent or insignificant.

Early signs

Unlike most diseases associated with a violation of the number of chromosomes, intrauterine development of children with Klinefelter's syndrome is normal, there is no tendency to premature termination of pregnancy. So in infancy and early childhood, it is almost impossible to suspect pathology. Moreover, the clinical signs of the classic Klinefelter syndrome appear, as a rule, only in adolescence. However, there are symptoms that suggest the presence of Klinefelter's syndrome in the prepubertal period:

• high growth (the peak of the increase in growth occurs between 5-8 years);
• long legs (disproportionate physique);
• high waist.

In some patients, there is some delay in the development of speech.

In adolescence, the syndrome is often manifested by gynecomastia, which, with this pathology, looks like a bilateral symmetrical painless enlargement of the mammary glands. Since this type of gynecomastia is often seen in perfectly healthy adolescents, this symptom is often overlooked. Normally, adolescent gynecomastia disappears without a trace within several years, while in patients with Klinefelter's syndrome, reverse involution of the mammary glands does not occur. In some cases, gynecomastia may not develop at all, and then the pathology is manifested by signs of androgen deficiency already in the postpubertal period.

Symptoms of androgen deficiency in Klinefelter syndrome

Androgen deficiency in Klinefelter syndrome is associated with gradual testicular atrophy, which leads to a decrease in testosterone synthesis. The degree of androgen deficiency varies dramatically.

First of all, attention is drawn to the external signs of hypogonadism:

• scanty facial hair or its complete absence;
• female-pattern pubic hair growth;
• no hair on the chest and other parts of the body;
• small volume of testicles (2-4 ml) and their dense consistency (pathognomonic sign).

Since gonadal degeneration usually develops in the postpubertal period, in most patients, the size of the male genital organs, with the exception of the testes, corresponds to age norms.

Patients may complain of a weakening of libido and a decrease in potency. Many men with Klinefelter syndrome do not have sex drive at all, and some, on the contrary, have a family and live a normal sex life. The most constant sign of pathology is infertility, it is this that most often becomes the reason for such patients to see a doctor. Klinefelter syndrome is found in 10% of men with azoospemia.

All patients with impaired spermatogenesis need to determine the karyotype to exclude or confirm the diagnosis of Klinefelter's syndrome.

Androgen deficiency leads to the development of osteoporosis, anemia and skeletal muscle weakness. In a third of patients, varicose veins of the legs can be observed.

Androgens affect metabolism, which is why patients with Klinefelter's syndrome are prone to obesity, impaired glucose tolerance and type 2 diabetes.

The predisposition of such patients to autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, autoimmune diseases of the thyroid gland, and others) has been proven.

Psychological features

The intelligence quotient in patients with classic Klinefelter's syndrome varies from values \u200b\u200bbelow the average to values \u200b\u200bsignificantly higher than the average. However, in all cases, there is a disproportion between the general level of intelligence and verbal abilities, so that often patients with a sufficiently high IQ experience difficulties in perceiving large volumes of material by ear, as well as in constructing phrases containing complex grammatical constructions. Such features cause a lot of trouble for patients during the training period and often continue to affect professional activities.

Data on the psychological characteristics of patients with Klinefelter's syndrome are rather contradictory, however, most experts assess patients as modest, timid people with somewhat low self-esteem and increased sensitivity. There is evidence of the propensity of patients with Klinefelter syndrome to homosexuality, alcoholism and drug addiction. It is difficult to say whether the mental characteristics in such patients are caused by the direct influence of a chromosomal abnormality, or whether it is a reaction to problems in the sexual sphere.

With regard to different cytogenetic variants of Klinefelter's syndrome, the rule is true that with an increase in the number of additional X-chromosomes, the number and severity of pathological symptoms increases.

Diagnostics of the Klinefelter syndrome

In many countries, Klinefelter's syndrome is often diagnosed even before the birth of a child, since many women of late childbearing age, due to the high risk of genetic defects in future offspring, use prenatal genetic diagnosis of the fetus. Often, prenatal detection of Klinefelter's syndrome is a reason for termination of pregnancy, including on the recommendation of doctors. In Russia, the analysis of the karyotype of the unborn child is extremely rare.

If you suspect Klinefelter's syndrome, a laboratory blood test is done to determine the level of male sex hormones. Differential diagnosis with other diseases occurring with manifestations of androgen deficiency is required. An accurate diagnosis of Klinefelter's syndrome is made based on the study of the karyotype (set of chromosomes) of the patient.

Research Needed to Confirm the Diagnosis

In all men with sharply increased concentrations of gonadotropins, it is necessary to exclude Klinefelter's syndrome, since often the first laboratory sign of this genetic pathology is an increase in the concentration of gonadotropins in the blood with a normal content of total testosterone.

Klinefelter's syndrome must be differentiated from other forms of primary hypogonadism. In any case, with an increase in the level of FSH in the blood, it is necessary to determine the karyotype to exclude, first of all, Klinefelter's syndrome.

Treatment

Treatment goals for Klinefelter syndrome:

• Restoring normal testosterone levels
• Restoration of sexual function
• Elimination of metabolic disorders

With clinically severe pathology, lifelong testosterone replacement therapy is required. Adequate therapy allows not only to improve the appearance and general well-being of the patient, but also to restore the ability to a normal sexual life. In addition, replacement therapy prevents the development of osteoporosis, relieves muscle weakness. At a young age, treatment should be started immediately after diagnosis. With Klinefelter's syndrome, it is better to use long-acting testosterone preparations:

• a mixture of testosterone esters in the form of an oil solution, injections of which must be done 2-3 times a month;
• testosterone undecanoate in the form of an oil solution - a depot preparation with a delayed release of the active substance - injections once every 3 months.

Hormone treatment in the presence of the X chromosome in men should be permanent. The dose of the drug is selected individually under the control of serum testosterone and LH levels.

Already developed gynecomastia in Klinefelter's syndrome does not undergo involution even in the case of adequate treatment, therefore, it is often necessary to resort to surgical correction (mastectomy).

For the prevention of comorbidities such as obesity and type 2 diabetes, patients are advised to adhere to a diet and monitor their own weight.

Patients with Klinefelter's syndrome should be monitored at least every 6–12 months. It should include the following studies:

• a complete blood count to assess the level of hemoglobin and hematocrit;
• hormonal blood test, including the determination of testosterone and LH (carried out against the background of drug therapy 1-2 days before the next injection of testosterone);

The male chromosome, the notorious Y, is different from the other 45 included in the normal human gene set. She doesn't have a mate. It is she who is more inherent in a variety of mutations. As some researchers say, in the near future, civilization will face the complete disappearance of this element. On the other hand, the latest research has shown that the reproductive process can easily proceed without the participation of this chromosome.

What do scientists say?

According to researchers, male chromosomes will disappear in the next ten million years. Of course, there can be no certainty about this, but the forecasts are confirmed by fairly reliable calculations. This will happen due to the loss of functionality by the DNA structure element.

Already today it is reliably known that male chromosomes differ significantly from others, including X, since they cannot exchange genetic information during the reproductive process. This led to the loss of hereditary material and the accumulation of various mutations transmitted between generations. However, scientists pay attention: the presence of this particular chromosome, or rather, its absence, will not become an obstacle for the establishment of offspring.

Latest research

Often after that, there is rather implausible information about space aliens, but not in our case. Scientists actually figured out exactly when chromosomes were formed as a tool for determining the sex of the fetus. Previously, it was believed that this happened for the first time three million centuries ago. Research work carried out in the recent past has shown: 166 million years before our time, both male and female chromosomes were absent in the gene pool of our kind.

Many adhere to the theory that sex (male, female) chromosomes have the same gene set as a source. In ancient times, the evolution of mammals led to the emergence of a gene, the allele of which became the basis for the male type of organism. The allele in modern science is called Y, the second began to be designated X. That is, in fact, in the beginning there were almost identical chromosomes, the difference was in one gene. Over time, Y became a carrier of genetic information, more useful for the male half of the genus, but not important or harmful for the female.

Some features of the human body

Researchers, finding out the specific characteristics of male and female chromosomes, found that Y is not able to recombine with X during gametogenesis, that is, at the moment when germ cells mature. Therefore, possible changes are provoked exclusively by mutations. Genetic information generated during such a process cannot be evaluated by natural mechanisms as marriage, and there is no dilution by gene variations. Consequently, the father gives the son the complete set - and so over and over again, generation after generation. Gradually, the number of modifications accumulates.

The process of maturation of germ cells is associated with division characteristic of spermatozoa. Each such division is another possibility of additional mutations accumulating in the male sex chromosome. The acidity of the environment in which this process takes place also plays a role - this factor additionally provokes unplanned mutations. Scientists have found that statistically Y is the most frequently damaged chromosome of the entire gene set.

It was, it was, it will be

At present, the number of genes on the Y chromosome, as scientists say, is not less than 45, but not more than 90. Specific estimates differ somewhat, it depends on the methods used by the researchers. But the female sex chromosome contains almost one and a half thousand genes. This difference is due to evolutionary processes that led to the loss of genetic information.

In the old days, scientists, studying the dynamics of the Y chromosome, estimated that, on average, about 4.6 genes were lost in one million years. If this progression continues in the future, completely genetic information through this object will cease to be transferred in the next ten million years.

An alternative approach

Of course, X and Y are chromosomes, the study of which, in principle, became available to mankind quite recently, therefore, mainly scientists have only theoretical calculations, without data confirmed by practical observations, which is always associated with a small probability of error and discrepancy. Already, some are convinced that the above opinion is incorrect.

Specialized research was carried out at the Whitehead Institute. Scientists, examining the male set of chromosomes, came to the conclusion that genetic decay has completely stopped. It was only an evolutionary stage associated with the characteristics of the human body, and at present a stable state has been achieved, which will remain so for at least ten million years.

How it happened

The aforementioned alternative study on the X and Y chromosomes involved sequencing 11 million base pairs of the male chromosome. The genetic data of rhesus monkeys were taken as experimental samples. The sequence obtained in the course of the work was compared with the corresponding part of the male chromosome of chimpanzees, and a sample of human genetic information was taken as a control. Based on the data obtained, it was possible to confirm the assumption of the constancy of the genetic content of the chromosomes of men for 25 million years.

One of the authors of this study, Jennifer Hughes, explained that Y (the designation for the male chromosome) lost only one gene, which is strikingly different from experimental samples obtained from macaques. This indicates that in the near future (however, it is possible to call this time intervals measured in millions of years only conditionally) time, no loss of the chromosome threatens humanity.

Is it scary?

Currently, scientists know exactly which chromosome is responsible for the sex of the unborn child: it depends on this very 23rd pair, which in the male body is not even represented by the same pair, because XX is characteristic for women, and XY for men ... Therefore, theories about the possible disappearance of Y cause many fears: will humanity die out then? Will we become same sex?

Scientists assure that there is no cause for concern. Not so long ago, studies organized at a scientific institute in Hawaii have clearly shown that healthy offspring is quite possible with two genes on the male chromosome - and this is applied to mice. This means that in the future it will be possible to completely bypass this chromosome, successfully multiplying without it. This also applies to the person. Scientists pay attention: such research results are important not only for those who fear for the fate of humanity in the distant future. It is quite possible that they will help find the answer to questions about eliminating male infertility.

How the experiment was conducted

The researchers' workflow involved interacting with the reproductive cells of male mice. They were worked on, leaving only two genes from the male chromosome. One of them is responsible for the formation of the male structure of the body, including hormonal development, spermatogenesis, and the second for the proliferation factor.

In the course of research, it became clear that the gene that determines the proliferation of spermogonia is the only gene that the reproductive system of mice really needs for the formation of offspring.

What happened next?

To test the results of their theoretical findings, in the laboratory, scientists fertilized mouse eggs using improved male chromosomes. For this, a high-precision method of intracytoplasmic injection was used. The embryos that developed were implanted into the female organism - into the uterus.

Statistics showed: 9% of all pregnancies were successful, and the offspring were born completely healthy. But if the reproductive process takes place with the participation of such a male mouse, whose chromosome has not been changed, the percentage of successful pregnancies without deviations in the development of the offspring is only 26%. This clearly indicates that the male sex chromosome in the future may become only a relic of the past millennia. Probably, it will be possible to find on other chromosomes such elements responsible for gene information that have a correspondence with the male chromosome. If you activate their functionality, the object in question will become completely redundant.

Oncology and genetics

Some time ago, studies were published, from which the dependence of the likelihood of developing malignant neoplasms and the loss of the male chromosome follows. This is sometimes observed in old age. First of all, leukocytes are affected. Scientists have also found that this is one of the causes of early death: men with gene changes usually die earlier, but women live longer.

For the first time, this phenomenon was described about half a century ago, but the consequences, as well as the reasons, to this day remain a secret for the public with seven seals. As part of a study in Sweden, blood samples were taken from 1153 people aged 70-84 years. Only blood samples from men were examined, and the sample was from people who were regularly observed in the clinics of the state at least from the age of forty. The data collected clearly showed that the loss of the male chromosome is characteristic of those whose life expectancy is approximately 5.5 years less compared to men who did not face such a change. If the number of leukocytes with altered gene information increased, the likelihood of death caused by malignant processes increased.

Stereotypes and reliable information

It is generally accepted that the Y is the chromosome that determines the sex of the child, and this exhausts its functions. In fact, the genetic information it stores is important for many functions. Scientists hope that it will be through the study of the characteristics of this chromosome that it will be possible to invent an effective drug against tumors. Doctors speculate that the loss of a chromosome with age leads to a weakening of the immune system. This, in turn, creates conditions for the growth of malignant cells.

Image from unc.edu

Each woman is not just a mystery, but a mosaic of cells with different sets of active chromosomes. A person has 23 pairs of chromosomes, and the chromosomes of one pair carry the same sets of genes. The exception is a pair of sex chromosomes. In men, one of them is called X, and the other is called Y, and they differ significantly in their sets of genes. The X chromosome is much larger than the Y chromosome and contains more genes. Both sex chromosomes of women are X, and they differ from each other in the same way as the chromosomes within the other 22 pairs. Each woman has two X chromosomes, and each man has only one, and so that they are equally active in women and men, the body regulates their work. For this, one of the X chromosomes is inactivated in all cells of the woman's body. Which of the two sex chromosomes will be disabled, for each cell the case decides, so that one X chromosome works in some of the cells of the woman's body, and the other one in the rest.

As a result of this mosaicism, women rarely develop diseases associated with damage to the X chromosomes. Even if a woman has an X chromosome with a defect in any gene, the other chromosome of the pair, working in half of the cells, saves the day and prevents the disease from manifesting. In order for the disease associated with damage to the X chromosome to "play out" at full power, a woman must get two whole copies of this chromosome with a defect in the same gene. This is an unlikely event. At the same time, if a man receives a defective X chromosome (it comes from the mother), she will not have a pair to compensate for the damage, and the disease will show itself.

The X chromosome, unfortunately for men, carries many vital genes, so its breakage is fraught with dire consequences. Color blindness, hemophilia, Duchenne myopathy, fragile X syndrome, X-linked immunodeficiency are just the most famous genetic diseases, from which men almost exclusively suffer.

Color blindness

It is a common misconception that only men can be color blind. This is not true, however, women who are color blind are much less common. Difficulties with distinguishing some colors are experienced by only 0.4 percent of women and about 5 percent of men. Color blindness is the loss or malfunction of one of the pigments associated with the recognition of light of a particular color. There are three such pigments in total, and they are sensitive to waves of red, green and blue. Any complex color can be thought of as a combination of these three. Each cone cell, which is in the retina and is responsible for color recognition, contains only one type of pigment. For reasons still unknown, problems with the work of pigments, with the help of which we distinguish between red and green, are more common than defects in the pigment necessary to correctly recognize blue.

The genes on the X chromosome are responsible for the synthesis of pigments. If a man got a chromosome with a defective gene that determines for recognition, for example, of a red color, then only this defective X chromosome will be active in all the cones of his retina - he simply does not have another. Therefore, such a man will not have cones that can correctly recognize the color red. The retina of a woman has a mosaic structure, and even if one of the X chromosomes carries a damaged gene, this chromosome will be active only in the part of the cones responsible for recognizing the corresponding color. In other cones, the second chromosome, which carries the normal gene, will be active. The perception of color in such a woman will be slightly altered, but still she will be able to distinguish all the colors that people usually distinguish.

Hemophilia

Another well-known disease associated with defects in genes on the X chromosome is hemophilia, a blood clotting disorder. After an injury, a complex system of reactions is triggered in the blood of a healthy person, leading to the formation of fibrin protein filaments. Due to the accumulation of these filaments, at the site of injury, the blood becomes thicker and clogs the wound. If any of the stages of the process is violated, the blood does not clot at all or does it too slowly, so that the patient may die of blood loss even after tooth extraction. In addition, patients with hemophilia suffer from spontaneous internal hemorrhage due to the vulnerability of the vessel walls.

The cascade of reactions that eventually leads to the formation of fibrin filaments and thickening of the blood is very complex, and the more complex the system, the more places where it can break. There are three types of hemophilia associated with defects in three genes encoding proteins involved in the cascade. Two of these genes are located on the X chromosome, so one in 5,000 men suffers from hemophilia, and only 60 cases of women have been recorded in history.

Duchenne myopathy

Another important gene located on the X chromosome is the gene for the protein dystrophin, which is required to maintain the integrity of muscle cell membranes. In Duchenne myopathy, the work of this gene is disrupted, and dystrophin is not formed. Men who inherit an X chromosome with such a damaged gene develop progressive muscle weakness, as a result of which boys with this disease cannot walk on their own by the age of 12. As a rule, patients die at the age of about 20 years due to respiratory disorders associated with muscle weakness. In girls who received an X chromosome with a faulty dystrophin gene, due to mosaicity, the protein is absent in only half of the body cells. Therefore, women who are carriers of the defective dystrophin gene suffer only from mild muscle weakness, and even then not always.

X-linked severe immunodeficiency

Patients with severe immunodeficiencies are forced to live in a completely sterile environment, because they are extremely vulnerable to infectious diseases. X-linked severe immunodeficiency occurs due to a mutation in a gene that codes for a common component of several receptors required for immune system cells to communicate. As the name of the disease suggests, this gene is also located on the X chromosome. Due to non-working receptors, the immune system develops incorrectly from the very beginning, its cells are few in number, function poorly and cannot coordinate their actions. Fortunately, this serious illness is rare, affecting one in 100,000 boys. In girls, the onset of the disease is almost unbelievable.

Brittle syndromeX chromosomes

Another important gene located on the X chromosome is the FMR1 gene, which is necessary for the normal development of the nervous system. The work of this gene can be disrupted due to a pathological process in which the number of repeated DNA fragments in the gene increases. The point is that exact copying of a repeating number of units is always difficult. Let's imagine that we need to carefully rewrite a long number in which there are many identical digits in a row - it is easy to make a mistake and write several digits more or less. It is exactly the same in DNA. When cells are dividing, when the DNA doubles, the number of repeats can change by accident. It is because of the increase in the number of repeats in a short DNA fragment on the X chromosome that a “fragile” region may appear, which is easily torn during cell division. The FMR1 gene is located near the fragile site, and its work is disrupted. As a result of this pathology, mental retardation occurs, which manifests itself in men with a “fragile” X chromosome more clearly than in women.

Is it always better to have twoX chromosome than one?

It seems that having two X chromosomes is more beneficial than one: there is less risk of disease due to bad genes. How about males with this sex chromosome composition: XXY? Can they be expected to have an advantage over males with normal XY sex chromosomes? It turns out that the composition of XXY chromosomes is not a blessing, but quite the opposite. Men with this set of chromosomes suffer from Klinefelter's syndrome, in which there are many pathologies, but there is no benefit.

Moreover, diseases are known that are characterized by even larger numbers of X chromosomes, up to five per genotype. Such pathologies are found in both women and men. In the presence of excess X chromosomes, all but one of them are inactivated. However, even if the extra X chromosomes do not work, the more there are, the more severe the disease. Interestingly, intelligence especially suffers from the presence of excess X chromosomes - each extra chromosome of this type leads to a decrease in IQ by an average of about 15 points. It turns out that having a spare version of the X chromosome is good, but not always (men do not get better from an additional X chromosome). Having many spare variants of this sex chromosome is not beneficial for women or men.

Why are additional inactive X chromosomes harmful, and why does each extra chromosome exacerbate the severity of the disease? First, the extra X chromosomes are not turned off immediately, but only after the first 16 days of embryo development. And the earlier a violation occurs during development, the more varied and numerous its manifestations will be. Therefore, extra chromosomes can have time to "harm" quite fundamentally, so that pathologies will manifest themselves in completely different areas.

Second, some genes on the inactivated X chromosomes somehow escape the shutdown. Although the X and Y chromosomes are very different, they still form a pair and have a small number of the same genes. If there are too many sex chromosomes, and these genes remain active on all of them, the gene balance in the cells is disrupted. Therefore, the more extra chromosomes, the more severe the disease.

The X chromosome carries many vital genes, and it is not surprising that its defects are extremely unpleasant. Women are naturally given the opportunity to “play it safe” due to an additional copy of the chromosome, which can reduce the severity of the disease. However, such a "spare" is good only in the singular, and all additional X-chromosomes lead to the development of severe pathologies. Well, men who do not have a second X chromosome have more risk from their very conception. Alas.

Yulia Kondratenko