Chromosome 2 This is the second largest chromosome. The highest density of snips is found in the region of the centromere, but there are practically no repeats here. It contains noticeably fewer genes per unit length than chromosome 1 and a number of other chromosomes. However, the number

Chromosome 3 This is another fairly large chromosome. Unlike chromosome 2, its centromere region contains few snips and repeats. The largest number of snips is located closer to the ends of this chromosome, and the largest number of genes is on the short arm.

Chromosome 4 Genes, repeats and snips are distributed quite evenly on chromosome 4 (with the exception of the centromere region, where they are all represented in small numbers). It is estimated that the total number of genes here is less than the average per unit length of the genome. Among the diseases

Chromosome 5 Most of the genes on this chromosome are concentrated in two regions of the long arm and one region of the short arm closer to its end. There are two regions located around the centromere that are enriched in snips. A number of serious diseases are associated with the genes of chromosome 5:

Chromosome 6 The density of both genes and snips is greatest in several regions on the short arm of this chromosome, but the repeats are distributed quite evenly along the chromosome (there are only a few of them in the centromere region). A number of human pathologies are associated with the genes of chromosome 6: diabetes,

Chromosome 7 The density of snips is greatest in the pericentromeric region of the long arm of this chromosome. But the genes are located fairly evenly along the chromosome, with the exception of one section in the middle of the long arm, which contains the largest number of them. Among

Chromosome 8 Most of the snips in this chromosome are concentrated at the end of the short arm, and at the end of the long arm there is a region highly enriched in genes. The number of disease-associated genes on chromosome 8 is relatively small. Among them are genes

Chromosome 9 Here, snips, repeats, and genes are distributed very unevenly along the chromosome. In addition, chromosome 9 is enriched in snips compared to other chromosomes (when calculating their number per unit length). Moreover, their largest number is concentrated in

Chromosome 10 This chromosome is average in the number of genes, repeating regions and snips it contains per unit length, but their distribution along the chromosome is far from uniform: several regions on the long arm are highly enriched in genes and snips. Among

Chromosome 11 At the end of the short arm and in the pericentromeric region of the long arm of this chromosome there is a concentration of genes. The content of snips is increased only in the area of ​​the end of the short arm, and along the chromosome it is relatively the same. Of the total number of genes of this

Chromosome 12 This chromosome is average in most respects. Genes are distributed very unevenly in it. A number of diseases are associated with them: adrenoleukodystrophy, amyloidosis, malignant non-Hodgkin lymphoma, rectal cancer, emphysema, enuresis,

Chromosome 13 The short arm of this chromosome has not yet been sequenced well. There is a concentration of snips in the region of the centromere on the long arm. Chromosome 13, relative to other chromosomes, is depleted in genes (on average there are only about 5 genes per 1 million letters). Most of them

Chromosome 20 Chromosome 20 became the third most fully sequenced human chromosome. In size, this chromosome makes up only about two percent of the genetic code of the human genome. Genes, repeats and snips are distributed very unevenly along the chromosome.

Chromosome 21 This chromosome is the smallest in size and information capacity (it accounts for no more than 1.5% of the entire human genome). But it was sequenced only after chromosome 22. The number of genes on chromosome 21 is relatively small. With a size of approx.

Chromosome 22 This chromosome's DNA was sequenced first (December 1999) and is therefore more fully described. In chromosome 22, only a few regions remained undeciphered (less than 3% of the DNA length). It contains about 500 genes and 134 pseudogenes. All these gene sequences

Chromosome X This is the female sex chromosome. The presence of two X chromosomes determines female gender. The pair for the X chromosome in men is the dead and short Y chromosome. In women, on one of the 2 X chromosomes, all those genes that do not have a pair on the Y chromosome are inactivated.

Chromosomal mutations (otherwise called aberrations, rearrangements) are unpredictable changes in the structure of chromosomes. They are most often caused by problems that occur during cell division. Exposure to initiating environmental factors is another possible cause of chromosomal mutations. Let's figure out what manifestations of this kind of changes in the structure of chromosomes can be and what consequences they have for the cell and the entire organism.

Mutations. General provisions

In biology, a mutation is defined as a permanent change in the structure of genetic material. What does "persistent" mean? It is inherited by the descendants of an organism that has mutant DNA. This happens as follows. One cell receives the wrong DNA. It divides, and two daughters copy its structure completely, that is, they also contain altered genetic material. Then there are more and more such cells, and if the organism proceeds to reproduction, its descendants receive a similar mutant genotype.

Mutations usually do not pass without leaving a trace. Some of them change the body so much that the result of these changes is death. Some of them force the body to function in a new way, reducing its ability to adapt and leading to serious pathologies. And a very small number of mutations benefit the body, thereby increasing its ability to adapt to environmental conditions.

Mutations are divided into gene, chromosomal and genomic. This classification is based on differences occurring in different structures of genetic material. Chromosomal mutations, thus, affect the structure of chromosomes, gene mutations affect the sequence of nucleotides in genes, and genomic mutations make changes to the genome of the whole organism, adding or subtracting an entire set of chromosomes.

Let's talk about chromosomal mutations in more detail.

What types of chromosomal rearrangements can occur?

Depending on how the changes are localized, the following types of chromosomal mutations are distinguished.

1. Intrachromosomal - transformation of genetic material within one chromosome.
2. Interchromosomal - rearrangements, as a result of which two non-homologous chromosomes exchange their sections. Non-homologous chromosomes contain different genes and do not occur during meiosis.

Each of these types of aberrations corresponds to certain types of chromosomal mutations.

Deletions

Deletion is the separation or loss of any part of a chromosome. It is easy to guess that this type of mutation is intrachromosomal.

If the outermost part of a chromosome is separated, the deletion is called terminal. If genetic material is lost closer to the center of the chromosome, such a deletion is called interstitial.

This type of mutation can affect the viability of the organism. For example, the loss of a section of a chromosome encoding a certain gene provides a person with immunity to the immunodeficiency virus. This adaptive mutation arose approximately 2,000 years ago, and some people with AIDS managed to survive only because they were lucky enough to have chromosomes with an altered structure.

Duplications

Another type of intrachromosomal mutation is duplication. This is the copying of a section of a chromosome, which occurs as a result of an error during the so-called crossover, or crossing over, during cell division.

A section copied in this way can maintain its position, rotate 180°, or even be repeated several times, and then such a mutation is called amplification.

In plants, the amount of genetic material can increase precisely through repeated duplications. In this case, the ability of an entire species to adapt usually changes, which means that such mutations are of great evolutionary significance.

Inversions

Also refers to intrachromosomal mutations. Inversion is a rotation of a certain section of a chromosome by 180°.

The part of the chromosome turned over as a result of inversion can be on one side of the centromere (paracentric inversion) or on opposite sides of it (pericentric). The centromere is the so-called region of the primary constriction of the chromosome.

Typically, inversions do not affect the external signs of the body and do not lead to pathologies. There is, however, an assumption that in women with an inversion of a certain part of chromosome nine, the likelihood of miscarriage during pregnancy increases by 30%.

Translocations

Translocation is the movement of a section of one chromosome to another. These mutations are of the interchromosomal type. There are two types of translocations.

1. Reciprocal is the exchange of two chromosomes in certain areas.
2. Robertsonian - fusion of two chromosomes with a short arm (acrocentric). During the Robertsonian translocation, short sections of both chromosomes are lost.

Reciprocal translocations lead to problems with childbearing in humans. Sometimes such mutations cause miscarriage or lead to the birth of children with congenital developmental pathologies.

Robertsonian translocations are quite common in humans. In particular, if a translocation occurs involving chromosome 21, the fetus develops Down syndrome, one of the most frequently reported congenital pathologies.

Isochromosomes

Isochromosomes are chromosomes that have lost one arm, but have replaced it with an exact copy of their other arm. That is, in essence, such a process can be considered deletion and inversion in one bottle. In very rare cases, such chromosomes have two centromeres.

Isochromosomes are present in the genotype of women suffering from Shereshevsky-Turner syndrome.

All types of chromosomal mutations described above are inherent in various living organisms, including humans. How do they manifest themselves?

Chromosomal mutations. Examples

Mutations can occur in sex chromosomes and in autosomes (all other paired chromosomes of the cell). If mutagenesis affects sex chromosomes, the consequences for the body are usually severe. Congenital pathologies arise that affect the mental development of the individual and are usually expressed in changes in the phenotype. That is, outwardly mutant organisms differ from normal ones.

Genomic and chromosomal mutations occur more frequently in plants. However, they are found in both animals and humans. Chromosomal mutations, examples of which we will consider below, manifest themselves in the occurrence of severe hereditary pathologies. These are Wolf-Hirschhorn syndrome, “cry the cat” syndrome, partial trisomy disease on the short arm of chromosome 9, as well as some others.

Cry of the cat syndrome

This disease was discovered in 1963. It occurs due to partial monosomy on the short arm of chromosome 5, caused by a deletion. One in 45,000 children is born with this syndrome.

Why did this disease get such a name? Children suffering from this disease have a characteristic cry that resembles a cat's meow.

When the short arm of the fifth chromosome is deleted, different parts of it may be lost. The clinical manifestations of the disease directly depend on which genes were lost during this mutation.

The structure of the larynx changes in all patients, which means that “cat cry” is characteristic of everyone without exception. Most people suffering from this syndrome experience a change in the structure of the skull: a decrease in the brain region, a moon-shaped face. In case of “cry the cat” syndrome, the ears are usually located low. Sometimes patients have congenital pathologies of the heart or other organs. Mental retardation also becomes a characteristic feature.

Typically, patients with this syndrome die in early childhood, only 10% of them survive to the age of ten. However, there have also been cases of longevity with the “cry of the cat” syndrome - up to 50 years.

Wolf-Hirschhorn syndrome

This syndrome is much less common - 1 case per 100,000 births. It is caused by the deletion of one of the segments of the short arm of the fourth chromosome.

The manifestations of this disease are varied: delayed development of the physical and mental sphere, microcephaly, characteristic beak-shaped nose, strabismus, cleft palate or upper lip, small mouth, defects of internal organs.

Like many other human chromosomal mutations, Wolf-Hirschhorn disease is classified as semi-lethal. This means that the viability of the body with such a disease is significantly reduced. Children diagnosed with Wolf-Hirschhorn syndrome usually do not live beyond the age of 1 year, but one case has been recorded in which the patient lived for 26 years.

Partial trisomy syndrome on the short arm of chromosome 9

This disease occurs due to unbalanced duplications in the ninth chromosome, as a result of which there is more genetic material on this chromosome. In total, more than 200 cases of such mutations in humans are known.

The clinical picture is described by delayed physical development, mild mental retardation, and a characteristic facial expression. Heart defects are found in a quarter of all patients.

With partial trisomy syndrome of the short arm of chromosome 9, the prognosis is still relatively favorable: most patients survive to old age.

Other syndromes

Sometimes chromosomal mutations occur even in very small sections of DNA. Diseases in such cases are usually caused by duplications or deletions, and are called microduplications or microdeletions, respectively.

The most common such syndrome is Prader-Willi disease. It occurs due to microdeletion of a section of chromosome 15. Interestingly, this chromosome must be received by the body from the father. As a result of microdeletions, 12 genes are affected. Patients with this syndrome have mental retardation, obesity, and usually have small feet and hands.

Another example of such chromosomal diseases is Sotos syndrome. A microdeletion occurs on the long arm of chromosome 5. The clinical picture of this hereditary disease is characterized by rapid growth, an increase in the size of the hands and feet, the presence of a convex forehead, and some mental retardation. The incidence of this syndrome has not been established.

Chromosomal mutations, more precisely, microdeletions in areas of chromosomes 13 and 15, cause Wilms tumor and retinblastoma, respectively. Wilms tumor is a kidney cancer that occurs primarily in children. Retinoblastoma is a malignant tumor of the retina that also occurs in children. These diseases are treatable if diagnosed in the early stages. In some cases, doctors resort to surgical intervention.

Modern medicine eliminates many diseases, but it is not yet possible to cure or at least prevent chromosomal mutations. They can only be detected at the beginning of fetal development. However, genetic engineering does not stand still. Perhaps soon a way to prevent diseases caused by chromosomal mutations will be found.

Currently, several clinically defined syndromes associated with abnormalities of chromosome 5 have been identified, one of which is called “cry of the cat” syndrome (monosomy on the short arm of chromosome 5).

In 1963, J. Lejen et al. , examining children with specific craniofacial dysmorphia and unusual crying, reminiscent of a cat's meow, they discovered a shortening of one of the chromosomes of group B. Subsequently, using differential staining methods, it was found that the patients had a deletion of the short arm of chromosome 5. Syndrome, Taking into account its main symptom - a specific child's cry associated with changes in the larynx (narrowing, softness of cartilage, swelling or unusual folding of the mucous membrane, reduction of the epiglottis), they began to call it the “cat cry” syndrome. This syndrome is more common than all other autosomal deletion syndromes. Its frequency is 1 in 45,000-50,000 births, and among mentally retarded children - 1.5 in 10,000. Cytogenetic studies reveal pronounced polymorphism: from the loss of a third to half the length of the short arm of chromosome 5. Loss of the entire short arm or a small fragment of it is rare. The clinical picture of the syndrome is associated with the loss of even a small section of the short arm of chromosome 5 (5p15.1-p15.2 ) . A correlation between the frequency of births of children with the syndrome and the age of the parents has not been identified. Girls are slightly more common than boys. The life expectancy of patients is not precisely established. In most cases, death occurs from associated infection, pneumonia and respiratory failure. Children are born with a slightly reduced body weight - 2500 g. Characteristic signs are: specific crying, mental and physical development retardation, microcephaly, low-lying deformed ears, microgenia, moon-shaped face, hypertelorism and anti-Mongoloid incision of the palpebral fissures, epicanthus, strabismus and muscle hypotonia. A third of patients have optic nerve atrophy. Diagnostic signs such as a moon-shaped face, “cat cry,” and muscle hypotonia gradually disappear with age, while microcephaly, strabismus, and retarded mental and physical development progress. Among the defects of internal organs, the most common are heart defects (septal defects, patent ductus batallus). In some cases, autopsy reveals arynencephaly, microgyria of the cerebral hemispheres, cerebellar hypoplasia, and internal hydrocephalus. There are malformations of the kidneys and gastrointestinal tract.

5.2.4. Trisomy chromosome 8

Trisomy 8, first described in the late 60s, has been fairly well studied. Currently, more than 200 cases have been described. Unlike all autosomal trisomies (Down, Edwards, Patau syndromes), in which complete forms of the disease mainly occur, mosaic forms predominate in trisomy 8. The minimum proportion of abnormal cells and the correlation between the severity of phenotypic manifestations and the ratio of trisomic and normal cells in the body of the affected child have not yet been established. Moreover, no clinical differences were found in the complete and mosaic forms of the disease, which allows us to combine these patients into one group. The population frequency of trisomy 8 is not precisely known. Among the patients, male children are more common (the approximate ratio of males to females is 5:2). Children are born full-term, with normal body weight. At birth and thereafter they do not lag behind in growth. There is moderate mental retardation. Obviously, this is due to the fact that about 90% of cases of trisomy 8 are represented by mosaic forms. A common symptom of this trisomy is brain damage. Basically, agenesis of the corpus callosum and hydrocephalus are observed. Children with trisomy 8 with a brain defect (especially with mosaic forms) live up to 12-17 years. Specific signs for this syndrome have been identified, which include a convex forehead, an inverted lower lip, aplasia of the patella, contractures, deep grooves between the interdigital pads, and defects of the urinary system (mainly hydronephrosis). Other signs include strabismus, epicanthus, high palate, micrognathia, deformed ears with abnormal lobes, short folded neck, camptodactyly, clinodactyly, scoliosis, abnormalities of the hip joints, clubfoot, inguinal hernias, cryptorchidism, heart defects and gastrointestinal tract defects. (atresia of the anus and esophagus). Less common are macrocephaly, wide nasal bridge, optic nerve atrophy, iris coloboma, cataracts, corneal opacities, accessory ribs, and closed spina bifida. Trisomy 8 is considered a clinically recognizable chromosomal syndrome.

5.2.5. Trisomy 9

There are descriptions of several dozen cases of trisomy 9 in the literature. There are three forms of this pathology: complete, mosaic and trisomy over the entire chromosome with the exception of the terminal segment of the long arm - 9q32 33->qter, that is, the trisomic chromosome is presented as The most pronounced clinical picture is observed with full form of trisomy 9 Children with this form of the syndrome are born with prenatal hypoplasia (birth weight less than 2000 g). The following signs are characteristic: delayed mental and physical development, microcephaly, wide sutures and fontanelles, enophthalmos (less often microphthalmos), fleshy bulb-shaped nose , microgenia, retromicrognathia, deformed low-lying ears, dislocation of the hips, abnormal position of the fingers, camptodactyly, clubfoot, contracture of large joints, in boys - hypoplasia of the penis and scrotum, cryptorchidism. Less common are clefts of the upper lip and palate, coloboma of the iris, opacification corneas, hypoplasia of the distal phalanges, dislocation of the head of the radial bones, duplication of the uterus. There are defects of internal organs - the heart (ventricular septal defect, patent ductus arteriosus, anomalies of large vessels), urinary system (cysts, unilateral agenesis or bilateral hypoplasia, hydronephrosis, duplication of the collecting system) , gastrointestinal tract (abnormal intestinal rotation, atresia of the bile ducts and anus), brain (defects of the corpus callosum and microgyria) Life prognosis depends on the degree of damage to internal organs and the form of the disease and varies - from several days to several pets Mosaic and with trisomy - its clinical course is easier for the part of the form compared to the full form. The severity and constancy of phenotypic manifestations allow us to speak of a clinically recognizable syndrome

5.2.6. Patau syndrome (trisomy 13)

Trisomy syndrome of chromosome 13 was first described by the American pediatrician and geneticist K. Patau, after whom this syndrome is named. In the population, it occurs with a frequency of -1 in 6000-12,000 births, sex ratio 1 1, the average age of parents is 32 for mothers, 32 for fathers - 34 years old Children with Patau syndrome are born with prenatal hypoplasia (body weight up to 2600 g) at a gestational age of 38-39 weeks, a characteristic complication of pregnancy is polyhydramnios. Clinical signs of the syndrome include microcephaly, trigonocephaly (skull with a wide occipital and narrow frontal parts), low sloping forehead, wide nose with a sunken bridge of the nose, narrow palpebral fissures, hypertelorism, microphthalmia (less commonly anophhalmia), iris coloboma, lens opacities, clefts of the upper lip and palate, polydactyly of the hands and feet, flexor position of the hands, “rocker foot” , cryptorchidism, hypospadias, hypoplasia of the penis, duplication of the uterus and vagina. Figure 5 2 a shows the phenotype of a child with Patau syndrome, and Figure 5 3 a (color tab) shows the result of molecular cytogenetic diagnosis of the mosaic form of Patau syndrome Among the anomalies of internal organs defects of the central nervous system (arynencephaly, holoprosencephaly, aplasia and hypoplasia of the corpus callosum, cerebellar hypoplasia, aplasia and hypoplasia of the optic nerves), cardiovascular system (defects of the interventricular and interatrial septa, defects of large vessels), digestive organs (mobile blind intestine, heterotopia of fragments of the spleen into the pancreas), urinary system (renal cysts, increased lobulation, hydronephrosis, hydro- and megaloureter, atresia and stenosis of the ureter, duplication of the ureter)

The main signs of Patau syndrome are cleft lip and

Fig. 5 2 a 6 f Phenotypes of children with (a) Patau (trisomy of chromosome 13), (b) Edwards (trisomy of chromosome 18), (c) Down (trisomy of chromosome 21) syndromes.

palate, scalp defects, which have a round shape up to 1-1.5 cm in diameter with a smooth bottom, represented by the aponeurotic helmet [ZO] The central nervous system is affected in all cases, with the most constant arynencephaly, aplasia and hypoplasia of the cerebellar vermis. In some cases, such gross defects as cyclopia, ethmocephaly (congenital underdevelopment of the nose), cebocephaly (“monkey face”), associated with holoprosencephaly, are observed. Children with Patau syndrome usually die before one year of age from severe, incompatible developmental defects. Children who live from 2-3 years and above suffer from deep idiocy.

5.2.7. Monosomy of the short arm of chromosome 17 (17p-)

In children with monosomy (deletion) of the short arm of chromosome 17, affecting the p11-13-»pter regions, severe malformations of the brain (lissencephaly and hypoplasia of the corpus callosum), as well as heart defects, are observed. Brachycephaly, wide face and bridge of the nose, hypoplasia of the midface, short arms, craniosynostosis are also noted; mental retardation associated with behavioral hyperactivity Effective diagnosis of telomeric and subtelomeric deletions of the short arm of chromosome 17 is carried out using the FISH method. The clinical symptoms of this syndrome were described independently by Miller and Dicker, since then in the literature one can find the name of this monosomy as Miller-Dieker syndrome (Miller-Dieker syndrome) or according to the main feature - lissencephaly syndrome. As a rule, the clinical diagnosis of the syndrome is established in the first days of a child’s life, and in some cases prenatally

5.2.8. Monosomy of the short arm of chromosome 18 (18p-)

Descriptions of about 200 cases of this disease are devoted to the characteristics of monosomy (deletion) of the short arm of chromosome 18 with loss of chromosomal material in the p 11 H>pter region. There are two main phenotypic variants of monosomy 18p: (1) - rarer with severe defects of the arynencephalic series (from cyclopia to arynencephaly), (2) - without these defects. In the second case, mental retardation, microcephaly, hypertelorism, ptosis, epicanthus, wide nasal bridge, microretrogenia, large dysplastic ears, cleft palate, short folded neck, clinodactyly of the little fingers, depressed chest, short stature, brain and heart defects are observed. alopecia, hip dislocations, spinal abnormalities. The life prognosis depends on the presence of gross defects of the arynencephalic series: children with such defects die in the first days and months of life. If there are no gross brain defects, then life expectancy is normal - patients aged over 60-65 years are described. Clinical signs of partial monosomy of the short arm of chromosome 18 are detected in the first years of a child’s life. In Fig. Figure 5.4 presents a child who, after molecular cytogenetic diagnostics, was diagnosed with short arm deletion syndrome of chromosome 18, the first phenotypic variant with karyotype 46,XY.ish del (18)(p11.1)(pBRHS13-).

5.2.9. Monosomy of the long arm of chromosome 18 (18q-)

In less detail, compared to 18p- syndrome, monosomies (partial deletions) of the long arm of chromosome 18 (18q-) with loss of chromosomal material in the q21-23^qter region are described. Currently, more than 100 cases of the syndrome have been described. In this case, the critical points for a certain clinical picture are q21-23. Children with monosomy 18q are characterized by mental retardation, growth retardation, epicanthus, strabismus, nystagmus, iris coloboma, hypertelorism, optic atrophy, cleft soft palate, deformed auricles (“satyr ears”) with a narrow auditory canal, hypospadias, cryptorchidism , scrotal hypoplasia, congenital heart defects. They note the peculiar shape of the face with a flattened back of a small nose, deep-set eyeballs, a thin upper lip and downturned corners (“carp” mouth). Defects of the central nervous system and kidneys are not very specific. Monosomy 18q has been called a clinically recognizable syndrome since the very first cases of its description.

5.2.10. Edwards syndrome (trisomy 18)

In 1960, J.H. Edwards et al. during a cytogenetic study of cells from patients with multiple congenital malformations, he discovered an additional autosome in the karyotype. This chromosome was later identified as 18 and trisomy was called Edwards syndrome. The frequency of this disease in the population is 1 case per 7000 births. Girls are affected much more often than boys. Children are born with prenatal hypoplasia (birth weight no more than 2300 g) during full-term or post-term pregnancy (43-45 weeks), usually complicated by polyhydramnios. Phenotypic manifestations are characteristic and diverse. These include dolichocephaly, microf-

Fig 5 4 a 6 (a) Phenetin of a child with short arm deletion syndrome of chromosome 18; (6/ karyotype 46,XY,ish del (18)(pBRS13-) after FISH diagnostics with missing DNA sample on the centromere region of chromosome 18.

thalmia, low-lying deformed ears, high palate, cleft palate, microgenia, microstomia, clitoral hypertrophy, hypospadias, cryptorchidism, limb anomalies (flexor position of the hands, short

Fig. 5 5 h 6 c (a) Premium case of ADHD syndrome (fetus in the 21st week of pregnancy after its termination); (6) karyotype of a fetus with trisomy for chremosome 18 - 47,XX,+18; (c) interphase FISH diagnosis of a mosaic case of Edwards syndrome (interphase cells with two and three chromosomes* 18 are visible).

cue and wide big toe, “rocker foot”, cutaneous syndactyly of the feet, clubfoot) (Fig. 5.2 b). Among the defects of internal organs, anomalies of the heart (defects of the interatrial and interventricular septa), digestion (atresia of the esophagus and gallbladder, incomplete intestinal rotation, ectopia of pancreatic tissue), urinary system (fusion and duplication of the kidneys and ureters, cysts, hydro- and megaloureter), central nervous system (hypoplasia of the cerebellum and corpus callosum). Other anomalies known include spina bifida, pulmonary hypoplasia, opacification of the cornea and lens, glaucoma, optic nerve atrophy and microcornea. Brain developmental disorders are found in all cases. Mainly, hypoplasia of the cerebellum and hypoplasia (aplasia) of the corpus callosum are encountered. During autopsy, changes in the structure of the olives of the medulla oblongata are constantly revealed: they are asymmetrical, thickened, and the tortuosity of the posterior genus of the dentate nuclei is reduced. Children die in the first year of life from pneumonia and urinary tract infections. In Fig. 5 5 a, b, c presents an observation of a prenatal mosaic case of Edwards syndrome (phenotype) with karyotype 47,XX,+18 (cytogenetic diagnostic results), as well as the result of molecular cytogenetic diagnostics

5.2.11. Down syndrome

Mongoloid idiopathy, first clinically described by the English physician J. Down in 1866 and again by P. Waardenburg in 1932, who suggested its connection with a chromosomal abnormality, is the most famous and well-studied nosological form. For the first time, trisomy 21 was discovered by J. Lejenne and colleagues in 1959. They provided a cytogenetic and clinical description of 9 children with this syndrome. Many monographs and articles are devoted to Down syndrome. The frequency of Down syndrome is on average 1-2 cases per 1000 live births. With the introduction of prenatal diagnostic methods into genetic practice, the frequency of the syndrome in recent years in civilized countries has decreased by 15%. The trend towards a decrease in frequency in all developed countries is associated with a decrease in the number of births in women of older age groups. There are three cytogenetic forms of the syndrome: regular trisomy (93% of all cases ), translocation (5%) and mosaic (2%) It has been shown that the critical segment responsible for the phenotypic manifestations of Down syndrome is located in the 21q22 region, with trisomy of which a typical clinical picture develops. The clinical diagnosis is not complicated and is established for newborns in maternity hospitals. In Fig. Figure 5 2 c shows the phenotype of a child with Down syndrome, and Figure 5 3 b (colored inset) shows the results of molecular cytogenetic diagnostics. The main clinical signs of the syndrome include mental retardation, muscular hypotonia, brachycephaly, epicanthus and mongoloid incision of the palpebral fissures, cataracts, Brushfield spots (white lesions on the border of the outer and middle third of the iris), strabismus, less often clouding of the cornea and lens, thick lips, thickened tongue with grooves (“folded tongue”), flat dorsum of the nose, narrow palate, deformed ears, excess skin on the neck, joint laxity, transverse line of the palm (“monkey groove”), clinodactyly of the little fingers Children are born at term with moderately severe prenatal hypoplasia (birth weight up to 3000 g) Among the anomalies of the internal organs, heart defects are noted (septal defects in combination with anomalies large vessels), gastrointestinal tract (atresia or stenosis of the duodenum, less often atresia of the rectum, anus, esophagus), urinary system (hypoplasia or dysplasia of the kidneys, cortical cysts, hydroureter, hydronephrosis), brain (hypoplasia of the superior temporal gyrus, ventral displacement of the cerebellum) In children with Down syndrome, profound mental retardation in the degree of imbecility is noted. Certain types of mental activity are affected to varying degrees. Verbal tasks are performed worse than non-verbal ones. They are obedient, easily make contact, imitate, increased suggestibility. Currently, on the basis of thorough psychological examination of these children, the principles of therapeutic correction are successfully developed, allowing them to adapt to life

5.2.12. Cat's eye syndrome (trisomy 22)

The syndrome of trisomy 22 was described in detail in the 70s and was called “cat eye syndrome” because of the vertical localization of the iris coloboma in these patients, which gives the appearance of cat eyes. Cytogenetically, the syndrome was characterized by an extra extra chromosome in the karyotype. It was previously shown that the full clinical form of the syndrome is caused by trisomy of the 22pter-»22q11 region and a small suchromatin region of the long arm of chromosome 13 (13q32->q34), and the critical segments are associated with breakpoints in 22q11 Cat's eye syndrome is rare in the population, the frequency it has not yet been determined. Mosaic forms of the disease are often encountered, when chromosome disjunction occurs in mitosis, and not in myosis. Children are born with prenatal hypoplasia (body weight up to 2800 g) with a normal pregnancy duration. The most constant signs of the disease are mental retardation (profound mental retardation), delayed physical development, microcephaly, exophthalmos, iris coloboma, strabismus, elongated filter, cleft palate, microretrogenia, beaked nose, low-lying auricles, preauricular fossae, thumb hypoplasia, cryptorchidism, hypospadias, muscle hypotonia Among the anomalies of the internal organs, there are defects of the heart, kidneys (unilateral aplasia or hypoplasia), and gastrointestinal tract (anal atresia). Brain defects (except for microcephaly) are not typical.

The diagnosis of the syndrome requires cytogenetic confirmation. Since its description, the participation of the entire chromosome 22 and material from other autosomes in clinical polymorphism has been discussed.

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Animals, plants and microorganisms are the most common objects of genetic research.1 Acetabularia acetabularia. A genus of unicellular green algae of the siphon class, characterized by a giant (up to 2 mm in diameter) nucleus... ... Molecular biology and genetics. Dictionary.

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A special qualitative state of the world is perhaps a necessary step in the development of the Universe. A naturally scientific approach to the essence of life is focused on the problem of its origin, its material carriers, the difference between living and nonliving things, and evolution... ... Philosophical Encyclopedia