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Mysteries of the fifteenth chromosome. Prenatal screening; chromosomal abnormalities Third female chromosome in pair 15

Masculine and feminine

The Prado Museum in Madrid has a pair of paintings by the 17th century court painter Juan Carreño de Miranda entitled "La Monstrua vestida" and "La Monstrua desnuda" ("The Dressed Monster" and "The Undressed Monster"). The paintings depict a very fat five-year-old girl, Eugenia Martinez Vallejo, not a beauty, but still not a monster. Something in her appearance is not as it should be: unusual plumpness for her age, small arms and legs, strangely shaped mouth and eyes. Apparently, she was exhibited at the circus for fun. At first glance, the doctor will say that this is a typical case of a rare genetic disease - Prader-Willi syndrome. Children with this syndrome are born loose with deathly pale skin, at first they refuse to breastfeed, but then they begin to eat like crazy. They are completely unfamiliar with the feeling of satiety, so they suffer from obesity. There is a known case where a child with Prader-Willi syndrome, sitting in the back seat of a car, ate 0.5 kg of raw bacon while his parents were driving from the store with groceries. People with this syndrome are characterized by short arms and legs, underdeveloped genitals and a slightly inhibited psyche. They often throw tantrums, especially if they are not given food, but they are also characterized by, as one doctor put it, "exceptional agility in solving puzzles" ( Holm V. et al. 1993. Prader–Willi syndrome: consensus diagnostic criteria. Pediatrics 91: 398–401 ).

Prader–Willi syndrome was first described in Switzerland in 1956. We could classify this syndrome with many other genetic diseases that I promised not to talk about in this book, because GENES ARE NOT INTENDED TO CAUSE DISEASE. But there is one thing associated with this syndrome interesting feature, revealing some principles of the genome. In the 1980s, doctors noticed that, like all other genetic diseases, Prader-Willi syndrome often occurs in the same families for several generations, but at times it manifests itself as a completely different disease - Angelman syndrome. The disease is so different that it could be called the antipode of Prader-Willi syndrome.

Harry Angelman was working as a doctor in Warrington, Lancashire, when he first identified the link between rare cases of so-called "puppet babies" and an inherited genetic disorder. Unlike Prader-Willi syndrome, children with Angelman syndrome are born with increased muscle tone, sleep poorly, are thin, hyperactive, and are characterized by a small head and a large mouth, from which an overly large tongue often protrudes. Their gait resembles marionettes, which is why they are often called that. They are also characterized by a constantly good mood, a smile from ear to ear and bouts of irrepressible laughter. Unfortunately, a cheerful disposition is accompanied by significant mental retardation. Often they don't even know how to talk. Children with Angelman syndrome are born less frequently than children with Prader-Willi syndrome, but very often both syndromes are observed in the same families in different generations ( Angelman H. 1965. "Puppet" children. Developmental Medicine and Child Neurology 7: 681–688 ).

As it soon became known, both syndromes were caused by problems in the same part of chromosome 15. The only difference was that in the case of Prader-Willi syndrome the defect was inherited from the father, while in the case of Angelman syndrome it was inherited from the mother.

This fact contradicts everything we have learned about genes since Gregor Mendel. We said that inheritance is based on a simple recording of information in the form of a genetic (digital in nature) code. Now we learn that genes carry not only the recipes for proteins, but also something like a stamp in a passport indicating the place of birth - imprinting. There is something special about the genes received from the mother and from the father that makes it possible to distinguish them, as if in one of the cases the text of the genetic code was written in italics. In some tissues, not both genes on different chromosomes work, but only the maternal or only the paternal one. Therefore, a mutation in the same gene can manifest itself differently, depending on whether it came from the father or from the mother, which is the case with Prader-Willi and Angelman syndromes. How cells distinguish paternal from maternal genes is not yet entirely clear, but some hypotheses are already beginning to emerge. Another interest Ask: for what reasons did imprinting of maternal and paternal genes arise during evolution, what advantages does this give to the organism and the population as a whole?

In the early 1980s, two groups of scientists working in Philadelphia and Cambridge simultaneously made an amazing discovery. They tried to get a mouse from only one parent. Since it was not yet possible to clone a mouse from somatic cells of the body at that time (the situation quickly began to change after the successful experiment with Dolly the sheep), a group of researchers in Philadelphia simply fused two pronucleoli of fertilized eggs together. When a sperm penetrates an egg, its nucleus with chromosomes remains adjacent to the nucleus of the egg for some time without merging with it. Such nuclei inside the egg are called pronucleoli. Clever scientists use pipettes to remove one of the nuclei and replace it with another. You can fuse the nucleoli from two eggs or from two sperm, resulting in an egg with a full set of chromosomes, but only from the father or only from the mother. In Cambridge, a different approach was used for this purpose, but the result was the same. And in both cases the experiment ended in failure. The embryos were unable to develop normally and soon died in the uterus.

In the case of maternal chromosomes, the embryo initially developed normally, but did not form a placenta, without which it quickly died. On the contrary, when only the paternal chromosomes were combined in the egg, a large placenta and embryonic coverings were obtained, but there was no embryo inside. Instead of an embryo, a disorganized mass of cells grew, in which no body parts could be distinguished ( Cell Nature 311: 374–376 ).

The results of the experiments allowed us to draw an unexpected conclusion: paternal genes are responsible for the development of the placenta, and maternal genes are responsible for the differentiation of embryonic cells into organs and body parts. Why did such a distribution of labor appear between paternal and maternal genes? Five years later, David Haig of Oxford claimed to know the answer to this question.

Interestingly, in cases where the placenta does not secrete active hormones, the relationship between the embryo and the maternal body is more friendly. In other words, although mother and fetus have a common goal, they often cannot agree on how to achieve it and what resources the mother should provide to her child. These debates continue after the birth of the child, during weaning, and indeed throughout all other years.

The embryo's genome is half made up of maternal genes, which can lead to a conflict of interest over whether the maternal genes should care more about the embryo or about the mother herself. The paternal genes of the embryo are not threatened by such a conflict. They are interested in the maternal body only from the point of view of providing food and shelter during the development of the embryo. In terms human society male genes simply do not trust female genes with such a crucial moment as the creation of the placenta, and take this process under their personal control. This is why embryos that were formed as a result of the fusion of two sperm nucleoli produced a placenta so well.

Based on his purely theoretical hypotheses, Haig made practical conclusions, which were very soon confirmed experimentally. Thus, he suggested that oviparous animals should not have imprinting of maternal and paternal genes, since inside the egg it is pointless for the embryo to argue with the mother’s body about the size of the yolk allocated for its sustenance. The embryo is outside the mother's body even before it has the opportunity to manipulate her body in any way.

Even in marsupials such as kangaroos, in which the placenta is a fold of skin on the abdomen, according to Haig's hypothesis, there should be no imprinting of genes. It is now known that Haig was right. Imprinting is characteristic only of placental mammals and angiosperms ( Haig D., Westoby M. 1989. Parent-specific gene expression and the triploid endosperm. American Naturalist 134: 147–155 ).

In addition, Haig soon noted with triumph that another case of imprinting had been recorded for a pair of genes in the mouse genome exactly where he had predicted: in the system for regulating the rate of embryonic growth. We are talking about a gene that encodes a small protein called IGF2, which resembles insulin. This protein is constantly found in embryonic tissues, but is absent in adult organisms. In the embryo, there is another protein, IGF2R, that attaches to the IGF2 protein, although the meaning of this interaction is not yet clear. Perhaps its task is to remove the IGF2 protein from the body. Now pay attention. Both genes IGF2 And IGF2R, are diversified by origin: the first is read only from the paternal chromosome, and the second - only from the maternal. Apparently, here we are seeing an example of a small confrontation between parental genes: the paternal gene tries to speed up the development of the embryo, and the maternal one slows it down ( Haig D., Graham C. 1991. Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell 64: 1045–1046 ).

According to Haig's theory, sexual imprinting should take place along such competing pairs of genes. A similar situation should manifest itself in the human genome. Human gene IGF2 on chromosome 11 is also read only from the paternal chromosome. There are cases when there are two copies of this gene on one chromosome, which causes Beckwith-Wiedemann syndrome. In this case, the heart and liver grow too large. In addition, the development of the embryo is often accompanied by the appearance of tumors. For the gene IGF2R imprinting has not been detected in humans, but it seems that another diversified gene has taken on this role, H19.

If two diversified genes do nothing but fight with each other, perhaps they could be turned off without harm to the body? Strange as this hypothesis may sound, it is possible. Disruption of both genes does not interfere with the development of a normal mouse embryo. We return to the topic that we have already considered with the example of chromosome 8, to the question of selfish genes, working exclusively for their own sake and not caring at all about the prosperity of the organism and the population. Many scientists believe that there is no rational grain in the sexual imprinting of genes in terms of benefits for the body. This is just another confirmation of the theory of selfish genes and sexual antagonism.

As soon as we start thinking in terms of selfish genes, unexpected ideas and hypotheses come to mind. Let's consider one of them. Embryos in the same womb, controlled by their father's genes, can behave differently depending on which set of genes they received. These competitive differences will be especially pronounced in cases where the eggs were fertilized by the seed of different fathers, which is quite common in nature. Competition between embryos may lead to the selection of more selfish paternal genes. From such reasoning it is very easy to move on to practice and experimentally test our guess. Mice are good subjects for research. Different species of mice differ significantly in their behavior. So, for females of the species Peromyscus maniculatus Promiscuity is typical, so in each litter you can find mice from different fathers. In a different form Peromyscus polionatus, females are monogamous and remain faithful to their only chosen one. All pups in a litter come from the same father.

What happens if we cross these two species of mice with each other? P. maniculatus And P. polionatus? Appearance offspring will depend on what species the male and female belonged to. If you take a male P. maniculatus(with promiscuity), then in the female P. polionatus The mice will be born incredibly large. If the father is monogamous P. polionatus, then in the female P. maniculatus The mice will be born very small. Did you get the gist of the experiment? Paternal genes of the species P. maniculatus developed under conditions of fierce competition in the womb for maternal resources with other embryos, some of which were not even their relatives. Maternal genes P. maniculatus, in turn, evolved in such a way as to allow the mother to reason with her overactive embryos.

Paternal and maternal genes of the species P. polionatus evolved in much less aggressive conditions, so the female of a given species did not have the means to resist the paternal genes of the species P. maniculatus, and paternal genes P. polionatus were not active enough for the embryos to take their toll in the womb of the female P. maniculatus. This led to the fact that in one experiment the mice were too large, and in the other they were underdeveloped. A vivid illustration of the topic of gene imprinting ( Dawson W. 1965. Fertility and size inheritance in a Peromyscus species cross. Evolution 19: 44–55; Mestel R. 1998. The genetic battle of the sexes. Natural History 107: 44–49 ).

No theory is without flaws. This theory is too simple to be plausible. In particular, this theory suggests that changes in diversified genes should occur quite frequently, since the temporary success of one of the genes in a pair of antagonist genes stimulates the development of the other gene. But comparison of diversified genes in different types did not confirm this guess. On the contrary, it turned out that such genes are quite conservative. It is becoming increasingly clear that Haig's theory explains only some cases of imprinting ( Hurst L. D., McVean G. T. 1997. Growth effects of uniparental disomies and the conflict theory of genomic imprinting. Trends in Genetics 13: 436–443; Hurst L. D. 1997. Evolutionary theories of genomic imprinting. In: Reik W., Surani A. (eds), Genomic imprinting, p. 211–237. Oxford University Press, Oxford).

Gene imprinting has surprising consequences. In men, the maternal copy of chromosome 15 contains a sign that it came from the mother. But in the next generation, in a daughter or son, the same chromosome will contain a sign of paternal origin. At some point, the sign of the chromosome must switch to the opposite one. There is no doubt that such a switch occurs, since this is the only way to explain Angelman syndrome. There is no visible damage to chromosome 15, just two chromosomes that behave as if they both came from the father. This is explained by the fact that at the right time the sign of the chromosome did not switch in the mother’s body. The occurrence of this problem can be traced back through generations and a mutation can be detected in a small region of DNA immediately adjacent to the diversified genes. This is the so-called imprinting center, which somehow indicates the origin of the chromosome. Gene imprinting is carried out using methylation, a biochemical process that we already discussed when considering chromosome 8 ( Horsthemke B. 1997. Imprinting in the Prader–Willi/Angelman syndrome region on human chromosome 15. In: Reik W., Surani A. (eds), Genomic imprinting, p. 177–190. Oxford University Press, Oxford).

As you remember, methylation of the “letter” C is carried out by the cell in order to turn off unnecessary genes and put selfish self-copying DNA sections under house arrest. But in the early stages of embryo development, during the formation of so-called blastocytes, chromosome demethylation occurs. The genes are then remethylated at the next stage of embryonic development, gastrulation. However, demethylation does not occur completely. Diversified genes somehow manage to escape this process, with either only the maternal gene or only the paternal gene being activated, while the other paired gene remains methylated (inactive). There are many versions of how this all happens, but so far there is not a single experimentally confirmed option ( Reik W., Constancia M. 1997. Making sense or antisense? Nature 389: 669–671 ).

It is the incomplete demethylation of diversified genes that makes mammalian cloning such a challenge. For example, toads can be cloned very simply by taking a nucleus from any cell in the body and placing it into an egg. But such a procedure cannot be performed with mammalian cells, since in any cell of both the female and male body some part of the genes important for the development of the embryo is necessarily turned off as a result of methylation. Therefore, soon after the discovery of the phenomenon of gene imprinting, it was stated that cloning a mammalian organism is in principle impossible. In a cloned embryo, diversified genes will be either turned on or off on both chromosomes, resulting in an imbalance in the development of the embryo. “Thus,” concludes the scientist who discovered gene imprinting, “successful cloning of mammals using somatic cell nuclei seems impossible” ( McGrath J., Solter D. 1984. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37: 179–183; Barton S. C., Surami M. A. H., Norris M. L. 1984. Role of paternal and maternal genomes in mouse development. Nature 311: 374–376 ).

However, completely unexpectedly, in 1997, a cloned sheep, Dolly, appeared in Scotland. Until now, the creators of Dolly and other clones that soon followed him are not entirely clear how they managed to circumvent the imprinting problem. It appears that the procedures to which a somatic cell was subjected before cloning erased all information about the origin of the chromosomes ( Jaenisch R. 1997. DNA methylation and imprinting: why bother? Trends in Genetics 13: 323–329 ).

The diversified region of chromosome 15 contains about eight genes. The gene, the absence of which leads to the development of Angelman syndrome, is called UBE3A. Immediately following it are two other genes that are considered the main candidates for the genes causing Prader-Willi syndrome. These genes are called SNRPN And IPW. Their role has not been fully established, but it can be assumed that a breakdown in the gene is to blame SNRPN.

Unlike other genetic diseases, these syndromes are not caused by mutations in the corresponding genes, but by other reasons. When an egg is formed in the ovaries, it usually receives one pair of chromosomes. In rare cases, a malfunction occurs during the separation of chromosomes, and two paired chromosomes end up in one egg. After fertilization of such an egg, it already contains three pairs of chromosomes: two from the mother and one from the father. This usually happens during late motherhood and usually ends with the death of the embryo. Only if the egg contains three chromosomes 21, which is the smallest human chromosome, does the embryo survive. In this case, a child is born with Down syndrome. In all other cases, the presence of an extra chromosome leads to such a disproportion of biochemical reactions in cells that the development of the embryo becomes impossible.

The egg is not so defenseless against the vicissitudes of fate. In the short period from fertilization to the beginning of embryo development, it can be freed from the extra chromosome. As a result, two paired chromosomes remain in the cell, as expected. But the mechanism for removing an extra chromosome does not take into account its origin, so the removal occurs randomly. Although random removal ensures that 66% of the time the cell gets rid of one of the maternal chromosomes, occasionally the paternal chromosome is removed and the embryo continues to develop with two maternal chromosomes. Again, as a rule, this does not have of great importance, but not in the case of chromosome 15. If there are two maternal chromosomes 15 in the egg, then two genes at once UBE3A, instead of one, are included in the work, but not a single gene works SNRPN. And as a result - Prader-Willi syndrome ( Cassidy S. B. 1995. Uniparental disomy and genomic imprinting as a cause of human genetic disease. Environmental and Molecular Mutagenesis 26: 13–20; Kishino T., Wagstaff J. 1998. Genomic organization of the UBE3A/E6-AP gene and related pseudogenes. Genomics 47: 101–107 ).

At first glance, the gene UBE3A doesn't seem that important. Its product is E3 ubiquinone ligase, a mid-level protein clerk of unclear function that functions in some skin tissues and lymph cells. Later, in 1997, three groups of scientists discovered that this gene is also turned on in brain tissue in both mice and humans. This is an important discovery! Both Prader-Willi and Angelman syndromes indicate certain organic damage to the brain of patients. Moreover, it turns out that many other diversified genes operate in the brain. In a study of the mouse brain, evidence was obtained that the frontal lobes develop to a greater extent under the control of maternal genes, while paternal genes are responsible for the hypothalamus ( Jiang Y. et al. 1998. Imprinting in Angelman and Prader–Willi syndromes. Current Opinion in Genetics and development 8: 334–342 ).

The imbalance was discovered through one subtle method, which involved creating "chimera" organisms. Chimeras in genetics are organisms obtained as a result of the fusion of cells of two genetically heterogeneous organisms. This happens in nature, including in humans. A person will never realize that he is a “chimera” unless a detailed genetic analysis is performed. Simply, two embryos at the earliest stages of development unite and continue to develop as one organism. This phenomenon can be considered as the opposite of the appearance of identical twins. Instead of two organisms with the same genome, the result is one organism whose cells contain chromosomes from two different genomes.

In laboratory conditions, it is quite easy to obtain a chimeric mouse. You just need to lightly compress the embryo cells onto early stage development. But researchers from Cambridge added something to this experiment: they combined a normal mouse embryo with an embryo obtained from an egg with two pairs of maternal chromosomes (in the egg they combined pronucleoli from this and another egg). The result is a mouse with an incredibly large head. In another experiment, a second embryo was obtained by fusion of two sperm nuclei, i.e., the second embryo contained only the paternal chromosomes. This time the chimeric mouse had a large body but a small head. In addition, the cells with maternal chromosomes were pre-treated in a special way, as a result of which scientists were able to determine their distribution in the embryo. It turned out that the striatum, cerebral cortex and hippocampus of the experimental mouse consisted mainly of cells controlled by maternal chromosomes, while such cells were almost absent in the hypothalamus. In the cerebral cortex, signals from the surrounding world are processed and behavioral reactions are formed. Paternal chromosomes turned out to be poorly represented in the brain, but they were much more numerous in muscle tissue. As for the brain, they have a significant effect on the hypothalamus, pituitary gland and previsual field.

These areas of the brain underlie the “limbic system,” which is responsible for regulating emotions. Robert Trivers jokingly said that the cerebral cortex takes care of communicating with relatives on the maternal side, while the hypothalamus acts as a completely selfish organ ( Allen N. D. 1995. Distribution of pathenogenetic cells in the mouse brain and their influence on brain development and behavior. Proceedings of the National Academy of Sciences of the USA 92:10782–10786; Trivers R., Burt A. 1999. Kinship and genomic imprinting. Results and problems in cell differentiation 25: 1–21 ).

Thus, if we viewed the placenta as an organ that male genes do not trust female genes, then female genes do not trust male genes to control brain development. If with our development things are the same as with mice, then you and I live with maternal thoughts and paternal character (this is true only to the extent that thoughts and character are inherited). In 1998, another sexually imprinted gene was discovered in mice that has a significant effect on maternal behavior in female mice. Females with a working gene Place behave like exemplary mothers. If this gene does not work, then outwardly the female mouse is no different from her friends until it comes to the birth of the mice.

These females make terrible mothers. They do not complete the creation of the nest, they do not return lost mice to the nest, they do not monitor their cleanliness and generally pay little attention to them. The pups of such females usually die. It is not known by what logic, but this gene is inherited on the paternal line. In the body, only the version of the gene that is located on the paternal chromosome works, while the maternal version of the gene is blocked ( Vines G. 1997. Where did you get your brains? New Scientist, 3 May: 34–39; Lefebvre L. et al. 1998. Abnormal maternal behavior and growth retardation associated with loss of the imprinted gene site. Nature Genetics 20: 163–169 ).

From the standpoint of Haig's theory of genetic conflict at the stage of embryo development, this fact is difficult to explain. An interesting theory to explain this phenomenon was proposed by the Japanese scientist Yoh Iwasa. He proposed that since the sex of the embryo is determined by the paternal chromosome (either the X or Y chromosome), then it is the male X chromosome that must work in female body, i.e., the characteristics of female behavior must be determined by the genes of the chromosomes on the father’s side. If the female chromosome X also works, then the effect of feminization will manifest itself in sons, and in daughters - with a vengeance. From here it is logical to conclude that behavioral sexual dimorphism must be controlled by male genes ( Pagel M. 1999. Mother and father in surprise genetic agreement. Nature 397: 19–20 ).

The best support for this idea came from a natural experiment studied and described by David Skuse and colleagues at the Institute of Child Health in London. Skuse observed eight girls aged 6 to 25 with Turner syndrome, a genetic disorder caused by the absence of part of the X chromosome. Men have only one X chromosome, but women have two, although only one of the X chromosomes works in all cells of the body , while the other is inactivated. In theory, the absence of part of the X chromosome in women should not lead to big problems. Indeed, women with Turner syndrome appear to be developed both physically and mentally, but they often have problems adapting to society.

Skuse and his colleagues decide to study the behavior of a larger number of patients with this syndrome and track the differences between those who inherited the defective chromosome from their father and those who inherited it from their mother. Twenty-five girls with a defect in their mother's X chromosome were more likely to fit into a group and showed "high communication skills and good practical skills, resulting in better relationships with the team," which distinguished them from girls with a defect in their father's X chromosome. Skuse and colleagues found this using standard tests for learning ability, as well as with the help of questionnaires for parents, which asked to assess: how caring the child is in relation to other people; whether he senses when someone is upset or angry; does he take into account the comments of adults in his actions; how capricious the child is and whether he can do without the attention of adults; how easy it is to calm him down when he's upset; Does he often unknowingly offend other people? does he obey his parents, etc. Parents were asked to give their daughter a rating for each question using a three-point system, after which the overall result was calculated. All girls with Turner syndrome were found to be more difficult than normal girls and boys their age, but the scores were almost twice as bad in children with a defect in their father's X chromosome than in children who inherited the defective chromosome from their mother.

Scientists have come to the conclusion that somewhere on the X chromosome there is a gene or genes with sexual imprinting, as a result of which these genes work only on the paternal chromosome and are always turned off on the maternal one. These genes have some influence on the child's social development, in particular, on his ability to correctly assess the feelings of other people ( Skuse D. H. et al. 1997. Evidence from Turner's syndrome of an imprinted locus affecting cognitive function. Nature 397: 19–20 ).

It now becomes clear why autism, dyslexia and other speech problems occur more often in boys than girls. Boys have only one X chromosome, inherited from their mother. Necessary genes on it can not only be damaged, but also turned off as a result of imprinting. At the time of this writing, such genes had not yet been discovered, although evidence of imprinting of other genes on chromosome X is known.

Indeed, on chromosome X in last years Several genes have been found whose mutations lead to dyslexia and/or epilepsy, but there is no data yet on the imprinting of these genes ( De Covel C. G. et al. 2004. Genomewide scan identifies susceptibility locus for dyslexia on Xq27 in an extended Dutch family. Journal of medical genetics 41: 652–657; Lu J., Sheen V. 2005. Periventricular heterotopia. Epilepsy & behavior 7: 143–149 ).

An even more important result is the resolution of a long-standing debate that has continued throughout the 20th century: what determines behavioral sexual dimorphism - nature or social conditions? Some scientists tried to reduce everything to heredity, denying the role of learning and social traditions; others saw the influence of society in everything and denied any inheritance of behavior. However, no one has ever denied the role of training and the influence of society. The debate revolved mainly around whether heredity has any influence on the behavior of men and women. I was just writing this chapter when my one-year-old daughter discovered a small plastic doll and screamed with delight. Her older brother had once made the same cry when he discovered a toy tractor. Like many parents, I can't believe that this difference in toy preference is caused by hidden influence society for a one-year-old child. Boys and girls by nature have different inclinations and interests. Boys are more competitive and show an interest in cars, weapons and action. Girls are more interested in the people around them, outfits and communication. It is not only the social structure that leads to the fact that men prefer cards and women prefer novels.

As confirmation of the above, one unfortunate incident that occurred in 1960 in the USA can be cited. As a result of a botched circumcision, a newborn boy's penis was seriously damaged. Doctors decided to amputate it and, in order to avoid the young man’s suffering, performed an operation to change the child’s sex, turning him into a girl through surgery and hormonal therapy. John became Joan and grew up (or grew up) with dolls and dresses. The girl grew up and turned into a young woman. In 1973, Freudian psychologist John Money published his conclusion that Joan had become a normally developed girl, which once again proved the inconsistency of theories about the genetic predetermination of the roles of men and women in society.

Until 1997, no one bothered to check this fact. When Milton Diamond and Keith Sigmundson tried to find Joan, they found a man happily married to his wife. His story was different from the one Monet told. The child constantly felt discomfort and a desire to wear trousers, play with boys and walk around while standing. When he was 14 years old, his parents told him about the misfortune that had happened, which the boy accepted with a sense of relief. He stopped taking hormones, changed his name to John again, started dressing and acting like a man, and agreed to have breast removal surgery. At 25, he married a woman and adopted her child. Thus, this case became a striking example of the inheritance of behavior between a man and a woman, even despite the deliberate influence of society. Observations of animals also indicate a hereditary basis for the behavioral reactions of males and females. The brain is an organ with an innate gender identity. Now this statement is supported by data from geneticists who have discovered sex preference genes and genes with sexual imprinting ( Diamond M., Sigmundson H. K. 1997. Sex assignment at birth: long-term review and clinical implications. Archives of Pediatric and Adolescent Medicine 151: 298–304 ).

The human body is a complex multifaceted system that functions at various levels. In order for organs and cells to work in the correct mode, certain substances must participate in specific biochemical processes. This requires a solid foundation, that is, the correct transmission of the genetic code. It is the underlying hereditary material that controls the development of the embryo.

However, changes sometimes occur in hereditary information that appear in large groups or affect individual genes. Such errors are called gene mutations. In some cases, this problem relates to the structural units of the cell, that is, to entire chromosomes. Accordingly, in this case the error is called a chromosome mutation.

Each human cell normally contains the same number of chromosomes. They are united by the same genes. Full set makes up 23 pairs of chromosomes, but in germ cells there are 2 times less of them. This is explained by the fact that during fertilization, the fusion of sperm and egg must represent a complete combination of all the necessary genes. Their distribution does not occur randomly, but in a strictly defined order, and such a linear sequence is absolutely the same for all people.

3 years later, the French scientist J. Lejeune discovered that impaired mental development in people and resistance to infections are directly related to the extra 21 chromosome. She is one of the smallest, but she has a lot of genes. The extra chromosome was observed in 1 in 1000 newborns. This chromosomal disease is by far the most studied and is called Down syndrome.

In the same 1959, it was studied and proven that the presence of an extra X chromosome in men leads to Klinefelter's disease, in which a person suffers from mental retardation and infertility.

However, despite the fact that chromosomal abnormalities have been observed and studied for quite a long time, even modern medicine is not able to treat genetic diseases. But methods for diagnosing such mutations have been quite modernized.

Causes of an extra chromosome

The anomaly is the only reason for the appearance of 47 chromosomes instead of the required 46. Medical experts have proven that the main reason for the appearance of an extra chromosome is the age of the expectant mother. The older the pregnant woman, the greater the likelihood of chromosome nondisjunction. For this reason alone, women are recommended to give birth before the age of 35. If pregnancy occurs after this age, you should undergo an examination.

Factors that contribute to the appearance of an extra chromosome include the level of anomaly that has increased globally, the degree of environmental pollution, and much more.

There is an opinion that an extra chromosome occurs if there were similar cases in the family. This is just a myth: studies have shown that parents whose children suffer from a chromosomal disorder have a completely healthy karyotype.

Diagnosis of a child with a chromosomal abnormality

Recognition of a violation of the number of chromosomes, the so-called aneuploidy screening, reveals a deficiency or excess of chromosomes in the embryo. Pregnant women over 35 years of age are advised to obtain a sample amniotic fluid. If a karyotype abnormality is detected, then to the expectant mother It will be necessary to terminate the pregnancy, since the born child will suffer from a serious illness throughout his life in the absence of effective treatment methods.

Chromosome disruption is mainly of maternal origin, so it is necessary to analyze not only the cells of the embryo, but also the substances that are formed during the maturation process. This procedure is called polar body diagnostics of genetic disorders.

Down syndrome

The scientist who first described Mongolism is Daun. An extra chromosome, a gene disease in the presence of which necessarily develops, has been widely studied. In Mongolism, trisomy 21 occurs. That is, a sick person has 47 chromosomes instead of the required 46. The main symptom is developmental delay.

Children who have an extra chromosome experience serious difficulties in mastering material in school, so they need an alternative teaching method. In addition to mental development, there is also a deviation in physical development, namely: slanted eyes, flat face, wide lips, flat tongue, shortened or widened limbs and feet, large accumulation of skin in the neck area. Life expectancy reaches 50 years on average.

Patau syndrome

Trisomy also includes Patau syndrome, in which there are 3 copies of chromosome 13. A distinctive feature is a disruption of the central nervous system or its underdevelopment. Patients have multiple developmental defects, possibly including heart defects. More than 90% of people with Patau syndrome die in the first year of life.

Edwards syndrome

This anomaly, like the previous ones, refers to trisomy. IN in this case We are talking about chromosome 18. characterized by various disorders. Mostly, patients experience bone deformation, an altered shape of the skull, problems with the respiratory system and cardiovascular system. Life expectancy is usually about 3 months, but some babies live up to a year.

Endocrine diseases due to chromosome abnormalities

In addition to the listed chromosomal abnormality syndromes, there are others in which a numerical and structural abnormality is also observed. Such diseases include the following:

  1. Triploidy is a rather rare disorder of chromosomes, in which their modal number is 69. Pregnancy usually ends in early miscarriage, but if the child survives, the child lives no more than 5 months, and numerous birth defects are observed.
  2. Wolf-Hirschhorn syndrome is also one of the rarest chromosomal abnormalities that develops due to deletion of the distal end of the short arm of the chromosome. The critical region for this disorder is 16.3 on chromosome 4p. Characteristic signs- developmental problems, growth delays, seizures and typical facial features
  3. Prader-Willi syndrome is a very rare disease. With such an abnormality of chromosomes, 7 genes or some parts of them on the 15th paternal chromosome do not function or are completely deleted. Signs: scoliosis, strabismus, delayed physical and intellectual development, fatigue.

How to raise a child with a chromosomal disorder?

Raising a child with congenital chromosomal diseases is not easy. In order to make your life easier, you need to follow some rules. First, you must immediately overcome despair and fear. Secondly, there is no need to waste time looking for the culprit, he simply does not exist. Thirdly, it is important to decide what kind of help the child and family need, and then turn to specialists for medical, psychological and pedagogical help.

In the first year of life, diagnosis is extremely important, since motor function develops during this period. With the help of professionals, the child will quickly acquire motor abilities. It is necessary to objectively examine the baby for vision and hearing pathologies. The child should also be observed by a pediatrician, neuropsychiatrist and endocrinologist.

The carrier of an extra chromosome is usually friendly, which makes his upbringing easier, and he also tries, to the best of his ability, to earn the approval of an adult. The level of development of a special child will depend on how persistently they teach him basic skills. Although sick children lag behind the rest, they require a lot of attention. It is always necessary to encourage a child's independence. Self-service skills should be instilled by your own example, and then the result will not be long in coming.

Children with chromosomal diseases are endowed with special talents that need to be discovered. This could be music lessons or drawing. It is important to develop the baby’s speech, play active games that develop motor skills, read, and also teach him routine and neatness. If you show your child all your tenderness, care, attentiveness and affection, he will respond in kind.

Can it be cured?

To date, it is impossible to cure chromosomal diseases; Each proposed method is experimental, and their clinical effectiveness has not been proven. Systematic medical and educational assistance helps to achieve success in development, socialization and acquisition of skills.

A sick child should be observed by specialists at all times, since medicine has reached the level at which it is able to provide necessary equipment And different kinds therapy. Teachers will use modern approaches in the education and rehabilitation of the child.

During the deciphering of the human genome, the characteristics of chromosomes are described:

Chromosome 1– The largest chromosome. It accounts for almost 10% of the human genome. The number of genes is about 3000. More than 160 genes are associated with a variety of diseases: Alzheimer's disease, Gaucher disease, breast duct cancer, cardiomyopathy, cataracts, ectodermal dysplasia, hypothyroidism, acute lymphoblastic leukemia, neuroblastoma, prostate cancer, atherosclerosis.

Chromosome 2– it contains fewer genes than the first chromosome. However, the number of diseases associated with mutations in the genes of this chromosome is quite large: cystinuria, diabetes, rectal cancer, fibromatosis, hypothyroidism, obesity, Parkinson's disease, thrombophilia, tibialis muscle dystrophy, autosomal recessive deafness - 9, limb muscle dystrophy 2b.

Chromosome 3– the genes contained in it are associated with more than 90 different diseases: cardiomyopathy, rectal cancer, colorectal cancer, hemolytic anemia, hypocalcemia, myeloid leukemia, B-cell lymphoma, myotonic dystonia, kidney carcinoma, schizophrenia.

Chromosome 4– the total number of genes is below average. Diseases associated with this chromosome include Parkinson's disease, phenylketonuria, hypochondroplosia, acute immune deficiency, and a tendency to alcoholism.

Chromosome 5– a number of serious diseases are associated with the genes of this chromosome: megaloplastic anemia, colorectal cancer, capillary hemangioma, corneal dystrophy, autosomal dominant deafness, acute leukemia, acute dystrophy, asthma, etc.

chromosome 6– diabetes, spinocerebral atrophy, hemolytic anemia, leukemia, thrombophilia, Parkinson’s disease, sensitivity to tuberculosis.

Chromosome 7– chronic granulomatosis, rectal cancer, cystic fibrosis, flabby skin, hemolytic anemia, dwarfism, myotonia congenita, pancreatitis, trypsinogen deficiency, coronary artery disease.

Chromosome 8– the number of genes is relatively small, mutations in them lead to diseases such as chondrosarcoma, epilepsy, hypothyroidism, susceptibility to atherosclerosis, Werner’s syndrome, spherocytosis, etc.

Chromosome 9– albinism, galactesemia, melanoma, porphyria, stomatocytosis, dystonia, basal cell carcinoma.

Chromosome 10– cardiomyopathy, renal hyperplasia, cataract, leukemia, glioblastoma, endocrine neoplasia, prostate adenocarcinoma, schizencephaly.

Chromosome 11– albinism, breast cancer, bladder cancer, prostate cancer, deafness, erythremia, acute combined immunodeficiency, male infertility, multiple myeloma, thalassemia, sickle cell anemia, osteoporosis, etc. The total number of diseases is quite large.

Chromosome 12– genes are distributed unevenly in it. Diseases: emphysema, enuresis, growth retardation, keratoderma, lipoma, hereditary myopathy, phenylketonuria, syndrome salivary glands and etc.

Chromosome 13–genes are not sufficiently sequenced, relative to other chromosomes it is depleted in genes. Revealed: bladder cancer, deafness, deficiency of blood clotting factors, muscular dystrophy, pancreatic cancer, Wilson's disease, etc.

Chromosma 14– Contains genes important for function immune system, mutations in the genes of this chromosome are associated with a number of serious diseases: early form of Alzheimer's disease, cardiomyopathy, spherocytosis, phenylketonuria, temperature-sensitive apoptosis, etc.

Chromosome 15– incompletely sequenced. A wide range of diseases have been identified: albinism, Bartter's syndrome, Bloom's syndrome, hypomelanosis, gynecomastia, leukemia, muscular dystrophy, epilepsy, schizophrenia, etc.

Chromosome 16– stomach cancer, erythrocytosis, myeloid leukemia, tyrosemia, polycystic kidney disease, ovarian carcinoma, tyrosemia, mucopolysaccharidosis, fish eye disease.

Chromosome 17– high gene content: sporadic breast cancer, rectal cancer, diabetes, hemolytic anemia, tongue cancer, myosthenic syndrome, acute leukemia, muscular dystrophy, neuroblastoma, ovarian cancer, epidermolysis bullosa.

Chromosome 18 – the total number of genes whose mutations are associated with pathologies is small: amyloidosis, rectal cancer, pancreatic cancer, lymphoma, epidermolysis bullosa, etc.

Chromosome 19– is the richest in GC nucleotide pairs; there are sequences homologous to sequences on 16 other human chromosomes. Pathologies associated with this mutation in this chromosome include: rectal cancer, myotonic dystrophy, coronary artery atherosclerosis, hypertrophic cardiomyopathy, myotonic dystrophy, lymphoblastic leukemia, idiopathic diabetes mellitus, etc.

Chromosome 20– is only about 2% of the human genome in size. The genes on this chromosome carry information about a number of diseases, ranging from obesity and eczema to dementia and cataracts. Mutations in the genes of chromosome 20 are associated with: heart disease, severe immune system disorders, asthma, skeletal dysplasia, diabetes and many others.

Chromosome 21- the smallest chromosome in size and information capacity (only 200 genes were found in it). It contains a section of 7 million nucleotide pairs (this is larger than the entire genome of the E.Coli bacterium) containing only one gene. When three copies of this chromosome are present, Down syndrome occurs. Mutations on this chromosome can cause Usher syndrome, holoproesencephaly, and some forms of malignant tumors.

Chromosome 22– most fully described (about 3% undeciphered), first sequenced (1999). It contains 500 genes. For this chromosome, the functions of about half of the genes have been established; about 160 genes show significant homology with mouse genes. Despite its small size and small number of genes, its pathology has been established in some genetic and oncological diseases. There are currently 27 known diseases caused by abnormalities in chromosome 22. Gene disruptions on this chromosome cause: cancer, susceptibility to schizophrenia, Parkinson's disease, serious heart abnormalities and nervous system. In leukemia and lymphoma, trisomy and monosomy, exchange of sections (translocations) of different chromosomes have been identified. The most famous example is the Philadelphia chromosome, formed as a result of a translocation between chromosomes 9 and 22. Trisomy (3 copies instead of 2) causes cat's eye syndrome (coloboma of the outer membrane), anal atresia, some malformations and mental retardation. Trisomy is the second leading cause of miscarriages in pregnant women.

Chromosome X– female sex chromosome, the presence of two X chromosomes determines the female sex, XY - male sex. There are few genes on the X chromosome, the following diseases are associated with them: breast cancer, prostate cancer, cardiomyopathy, epilepsy, hemophilia B, ichthyosis, Barth syndrome, mucopolysaccharoidosis 2.

Y Chromosome– the male sex chromosome, it contains very few genes, less than 100. The mutation rate in this chromosome is 4 times higher than in the X chromosome. It contains a large number of palimdromes. The main role of those genes that are present is to control sex differentiation, the formation of testicles and the processes of spermatogenesis. In particular, the main “maleness” gene called SRY encodes a protein that turns on many genes of other chromosomes and thereby causes a cascade of biochemical reactions ( the final result is the formation of testicles). Today, this is the most conservative gene within the species. There have been cases when cells have not one, but two or even three copies of the Y chromosome. With this pathology, antisocial behavior and various psychological disorders appear in 35% of patients . Very few genes are associated with human diseases. The main ones are gonadal dysgenesis and Sertoli cell syndrome

25 Chromosome (mitochondrial genome)– mit-DNA is sometimes called chromosome 25 or M chromosome. This DNA was sequenced back in 1981. In a human cell, there are from 100 to 1000 mitochondria, each of which contains from 2 to 10 molecules of circular mi-DNA. It is characterized by a very compact arrangement of genes, as in the bacterial genome; it also has some differences from nuclear DNA. mitDNA is responsible for the synthesis of only a few, but very important proteins. It has been noticed that mitochondria in DNA are more vulnerable than the DNA genome. A connection has been found between mutations in mitDNA with the occurrence of cancer (breast cancer, lymphoma), as well as with some severe hereditary diseases.

One of the important results of studying the human genome is the emergence and rapid development of molecular medicine, which is based on the genetic uniqueness of each person.

In the section on the question chromosome pair 15 asked by the author Arina the best answer is It is believed that the 15th pair is responsible. for oncological problems.
Here is an example from the abstract. But my opinion is the same. We are talking about a group of chromosomes, not a pair.
Acrocentric chromosomes of group IV (D, 13-15 pairs) and group VII (G, 21-22 pairs) on the short arm carry small additional structures, the so-called satellites. In some cases, these satellites cause chromosomes to adhere to each other during cell division in meiosis, resulting in uneven distribution of chromosomes. One sex cell has 22 chromosomes, and the other has 24. This is how monosomies and trisomies arise for one or another pair of chromosomes. A fragment of one chromosome can join a chromosome of another group (for example, fragment 21 or 22 joins 13 or 15). This is how translocation occurs. Trisomy of chromosome 21 or translocation of its fragment is the cause of Down syndrome.

The frequency of congenital malformations is 2-3%, another 5% of newborns have so-called minor anomalies. Their causative factors are heterogeneous and include chromosomal abnormalities, monogenic diseases, the influence of teratogens, maternal diseases (insulin-dependent diabetes mellitus, phenylketonuria), infections (rubella, cytomegaly, etc.). But most congenital malformations are multifactorial, i.e. depend on a combination of genetic factors and exposure to aggressive environmental factors.

What is prenatal screening

Prenatalscreening, diagnosis and treatment is relative new problem in obstetrics. The origin of prenatal screening was perhaps the era of ultrasound in obstetrics, which began about two decades ago. With the discovery of new genes and their phenotypes, prenatal genetic diagnosis is becoming increasingly possible. It is necessary to distinguish between the concepts of screening and diagnosis.

Prenatal screening identifies individuals at high risk for complications from a population of individuals at low risk for complications. The specificity and sensitivity of screening tests are very important given the possibility of false-positive and false-negative screening results.

Prenatal diagnosis is, of course, more specific than screening (for example, amniocentesis or chorionic villus sampling), but also has a greater risk of complications. The first step in determining the risk to the fetus is to screen the mother for certain conditions or diseases.

The question often arises about the likelihood of an increase in frequency in the offspring of married couples who received treatment for infertility. Severe oligospermia and azoospermia are associated with balanced chromosome translocations (3-5%), Klinefelter syndrome (47, XXY), abnormalities and microdeletions of the Y chromosome.

X chromosome abnormalities (XXY, XXX, X mosaicism in Turner syndrome) are associated with reduced fertility (subfertility), as well as an increased risk of chromosomal abnormalities in offspring. In 2/3 of patients with congenital absence of the vas deferens, there is at least one mutation of the gene that is responsible for the development of cystic fibrosis. So, these patients should be screened for cystic fibrosis. In these patients, intracytoplasmic sperm injection is usually indicated, although the presence of a cystic fibrosis gene mutation may influence reproductive intentions.

Chromosomal abnormalities

Advanced maternal age is a risk factor for chromosomal abnormalities due to an increased possibility of chromosome nondisjunction during meiosis. Fertilization of a gamete with one extra chromosome results in a fertilization product with 47 chromosomes. Consequently, the frequency of aneuploidy—the number of chromosomes in the fertilization product, greater or less than 46—is increasing. Chromosome nondisjunction can occur in autosomes (trisomy 21, 13, 18) or sex chromosomes (monosomy 45, X, or trisomy 47, XVV, 47, XXX and etc). Unbalanced chromosome translocations are accompanied by an abnormal amount of chromosomal material (the whole chromosome or part thereof). The risk to the child depends on the type of translocation.

Risk factors for having children with chromosomal abnormalities

  • Mother's age 35 years or older
  • Birth of children with a history of chromosomal abnormalities
  • Chromosomal abnormalities in parents, including balanced translocations, aneuploidies, mosaicism
  • Chromosomal abnormalities in close relatives
  • Abnormal findings on ultrasound fetal anatomy
  • Abnormal serum screening test results/abnormal triple test (AFP, estriol)
  • History of birth of children with neural tube defects

The frequency of chromosomal abnormalities in live newborns is 0.5%, in stillborns - 5%, in spontaneous abortions - 50%. A common chromosomal abnormality is aneuploidy—an increase or deficiency of one chromosome. The most common chromosomal abnormalities in live births are trisomy 21 (1:800), trisomy 18 and trisomy 13.

Trisomy 16 most often leads to spontaneous miscarriages, and in the case of trisomy 18, stillbirth occurs in most cases. If there is a history of trisomy in the fetus, the risk of relapse during a second pregnancy is 1%. In the case of triploidy, spontaneous abortion or gestational trophoblastic disease usually occurs. In rare cases, a child may be born with triploidy, but life expectancy does not exceed 1 year.

Chromosomal abnormalities are often accompanied by pronounced phenotypic manifestations and congenital malformations, although they cannot always be detected by ultrasound screening.

The most accurate method for diagnosing chromosomal abnormalities is to study the fetal karyotype. For some chromosomal syndromes (Down syndrome), there are screening tests, such as the triple test:

1) level of a-fetoprotein;

3) the level of hCG beta subunit in the mother’s blood serum.

Down syndrome

Screening for genetic diseases

Today, more than 11,000 monogenic diseases are known, which are encoded by a single gene (genetically determined) and transmitted from parents to their offspring. The mechanism of transmission of many genetic diseases is explained by Mendelian principles.

Autosomal dominant monogenic syndromes occur with a frequency of 1: 200 individuals; the disease is observed in many generations, is transmitted to descendants and recurs with a frequency of 50%. Examples of autosomal dominant monogenic disorders include:

  • achondroplasia,
  • neurofibromatosis,
  • Marfan syndrome,
  • Huntington's disease,
  • familial polyposis.

The appearance of autosomal dominant diseases in newborns from “healthy” parents may be due to the following reasons:

1. Mosaicism of germ cells. A mutation can only occur in a population of germ cells. So, parents are unaffected, but can pass the mutation on to their offspring.

2. New mutations. Increasing parental age is associated with an increased risk of autosomal dominant disorders (achondroplasia, thanatophoric dysplasia, neurofibromatosis, Apert syndrome - craniosynostosis). The risk of relapse does not increase in other children.

3. Variable expression. The severity of the disease may vary, and mild and subclinical mutations may not be recognized by parents.

4. Reduced penetrance. Parents may have an abnormal gene without clinical manifestations of the disease.

5. Incorrect paternity. The frequency of incorrect paternity reaches 15%.

Autosomal recessive monogenic diseases appear in numerous relatives in the presence of two affected alleles. If both parents are carriers of the affected gene, the risk of the disease in the offspring is 25% in each pregnancy. Autosomal recessive diseases include cystic fibrosis, sickle cell anemia, phenylketonuria, Tay-Sachs disease, Canavan disease, and others.

In X-linked recessive syndromes (hemophilia, etc.), the carrier mother of the affected gene passes it on to her sons. So, 50% of sons may be sick and 50% of daughters will be carriers of this gene. Rare X-dominant syndromes can be passed on from each parent to each child, similar to autosomal dominant syndromes. The phenotype can vary greatly due to mixed penetrance, lyonization (heterochromatization) of the X chromosome (fragile X syndrome) and genomic imprinting.

Expansiontrinucleotide repeats. Some genes contain regions of triple repeats (for example, CCC). Such areas are unstable and can increase in subsequent generations; this phenomenon is called anticipation. The number of repetitions determines the degree of damage to the individual. Trinucleotide repeat expansions form the basis of numerous genetic disorders, such as fragile X syndrome, myotonic dystrophy, and Huntington's disease.

Syndromefragile (fragile) X chromosome It is the most common cause familial mental retardation. Affected males have typical features: large ears, protruding jaw, large testicles, autistic behavior, and mild to moderate mental retardation. Women are usually less affected due to X chromosome inactivation.

The fragile X gene is localized on the X chromosome and has three nucleotide repeats (NFRs). Normal individuals have 6-50 repeats, unaffected female carriers may have 50-200 repeats, which can spread through meiosis to complete mutation if more than 200 repeats are present. If a complete mutation occurs, the gene is inactivated by methylation; the fetus will be affected. The severity of the disease depends on the degree of X-inactivation in women, the degree of methylation and mosaicism of repeat size.

Female carriers of the premutation have a 50% risk of transmitting the gene with expansion. Males with the premutation are phenotypically normal, but all of their daughters will be carriers of the premutation. In the case of transmission to men, the number of repetitions remains stable. The X-chromosome breakage test is performed to determine the number of repeats and the degree of methylation.

Indications for Fragile X testing

  • Individuals with mental and general developmental delays, autism
  • Individuals with fragile X chromosome traits
  • Individuals with a family history of fragile X syndrome
  • Individuals with a family history of undiagnosed mental retardation
  • Fetuses from carrier mothers

Genomicimprinting- a process in which gene activation occurs predominantly in the maternal or predominantly in the parental chromosome, but not in both chromosomes. Normal development occurs only if both copies (maternal and paternal) of the imprinting gene are present. The imprinting gene is inactive, which means that the active gene is lost (by deletion) or receives a mutation, in which case the fetus will be affected. Only a few genes can experience imprinting.
Examples of genomic imprinting include Angelman syndrome and complete hydatidiform mole (a variant of gestational trophoblastic disease).

SyndromeAngelman characterized by severe mental retardation, ataxic gait, typical face, paroxysms of laughter and convulsions. The Angelman syndrome gene is active only on the maternally inherited chromosome, therefore, if a deletion of maternal chromosome 15 occurs or the maternal copy of the gene has a mutation, protein product does not form and the fetus will be affected.

Angelman syndrome can also develop if both copies of chromosome 15 are inherited from the father (absence of a maternal copy of chromosome 15). This condition is called uniparental disomy. Uniparental disomy occurs more often due to the loss of a chromosome in an embryo with trisomy or the addition of a chromosome in a fetus with monosomy for this chromosome. Each of the chromosomes can be genetically different (heterodysomy) or identical (isodisomy), depending on when this phenomenon occurs - during the first or second meiotic division, respectively.

Fullhydatidiform mole usually diploid (46, XX or X¥), but may be entirely paternal in origin, with no maternal chromosomal material. Under such conditions, the fetus cannot develop. Complete hydatidiform mole may accompany normal multiple pregnancy, but in this case the risk of maternal complications (hyperthyroidism, preeclampsia, premature birth) increases. Unlike a complete hydatidiform mole, a partial hydatidiform mole is usually triploid (69, XXX, 69, XVV), with an additional set of paternal chromosomes.

Triploidy with an additional set of maternal chromosomes occurs in IUGR fetuses, congenital defects development and small placenta.

Mitochondrial inheritance

Mitochondria in the cytoplasm of the egg (but not the sperm) are passed on from the mother to her offspring. The mitochondrion has its own DNA. There are several genetic diseases caused by mutations in mitochondrial DNA - Leber's hereditary optic neuropathy, Leigh's disease (subacute necrotizing encephalomyelopathy), and jagged red fiber myoclonic epilepsy. The expression of these diseases is variable.