1. Reveal the mechanisms that ensure the constancy of the number and shape of chromosomes in all cells of organisms from generation to generation?

Response elements:

1) due to meiosis, gametes with a haploid set of chromosomes are formed;

2) during fertilization, the diploid set of chromosomes is restored in the zygote, which ensures the constancy of the chromosome set;

3) the growth of the organism occurs due to mitosis, which ensures the constancy of the number of chromosomes in somatic cells

2. It is known that the Golgi apparatus is especially well developed in the glandular cells of the pancreas. Explain why.

Response elements:

1) pancreatic cells synthesize enzymes that accumulate in the cavities of the Golgi apparatus;

2) in the Golgi apparatus, enzymes are packaged in the form of vesicles;

3) from the Golgi apparatus, enzymes are carried into the pancreatic duct.

3. The total mass of mitochondria in relation to the mass of cells of various rat organs is: in the pancreas - 7.8%, in the liver - 18.4%, in the heart - 35.8%. Why do the cells of these organs have different mitochondrial content?

Response elements:

1) Mitochondria are the energy stations of the cell; ATP molecules are synthesized and accumulated in them;

2) intensive work of the heart muscle requires a lot of energy and therefore the content of mitochondria in its cells is the highest;

3) in the liver the number of mitochondria is higher compared to the pancreas, since it has a more intense metabolism.

4.What division of meiosis is similar to mitosis? Explain how it is expressed and what set of chromosomes in the cell it leads to.

Response elements:

1) similarities with mitosis are observed in the second division of meiosis;

2) all phases are similar, sister chromosomes (chromatids) diverge to the poles of the cell;

3) the resulting cells have a haploid set of chromosomes.

5. In what cases does a change in the DNA nucleotide sequence not affect the structure and function of the corresponding protein?

Response elements:

1) if, as a result of a nucleotide replacement, another codon encoding the same amino acid arises;

2) if the codon formed as a result of a nucleotide replacement encodes a different amino acid, but with similar chemical properties that does not change the structure of the protein;

3) if nucleotide changes occur in intergenic or non-functioning regions DNA.

6. What features of chromosomes ensure the transmission of hereditary information?

Response elements:

2) capable of self-duplication due to DNA replication;

3) are able to be evenly distributed in cells during division, ensuring the continuity of characteristics.

7. Explain the similarities and differences between mutational and combinational variability.

The problem solution scheme includes:

1) similarities: mutational and combinational variability affect the genotypes of the organism and are inherited;

2) differences: mutations - changes in the genotype are caused by changes in hereditary structures (genes, chromosomes, genome);

3) with combinative variability, different combinations of genes arise.

Chromosomes(Greek chrōma color, color + sōma body) - the main structural and functional elements of the cell nucleus, containing genes. The name "chromosomes" is due to their ability to be intensely stained with basic dyes during cell division. Each biological species is characterized by the constancy of the number, size and other morphological characteristics of the chromosome. The chromosome set of germ and somatic cells is different. Somatic cells contain a double (diploid) set of chromosomes, which can be divided into pairs of homologous (identical) chromosomes, similar in size and morphology. One of the homologues is always of paternal origin, the other is of maternal origin. In the sex cells (gametes) of eukaryotes (multicellular organisms, including humans), all chromosomes of the set are represented in the singular (haploid chromosome set). In a fertilized egg (zygote), the haploid sets of male and female gametes are combined in one nucleus, restoring a double set of chromosomes.
In humans, the diploid chromosome set (karyotype) is represented by 22 pairs of chromosomes (autosomes) and one pair of sex chromosomes (gonosomes). Sex chromosomes differ not only in the composition of the genes they contain, but also in their morphology. The development of a female individual from a zygote is determined by a pair of sex chromosomes consisting of two X chromosomes, that is, the XX pair, and the male is determined by a pair consisting of an X chromosome and a Y chromosome, that is, the XY pair.

The physicochemical nature of the chromosome depends on the complexity of the organization of the biological species. Thus, RNA-containing viruses have role chromosomes. performed by a single-stranded RNA molecule; in DNA-containing viruses and prokaryotes (bacteria, blue-green algae), the only chromosome is a DNA molecule free of structural proteins, closed in a ring, attached by one of its sections to the cell wall. In eukaryotes, the main molecular components of chromosomes are DNA, the basic proteins histones, acidic proteins, and RNA (the content of acidic proteins and RNA in the chromosome varies at different stages of the cell cycle).
DNA in the chromosome exists in the form of a complex with histones, although individual sections of the DNA molecule may be free of these proteins.

DNA complexes with histones form the elementary structural particles of the chromosome - nucleosomes. With the participation of a specific histone, the nucleosomal thread is compacted; individual nucleosomes are closely adjacent to each other, forming a fibril. The fibril undergoes further spatial packing to form a second-order filament. Loops are formed from second-order threads, which are third-order structures of chromosome organization.

The morphology of chromosomes is different in individual phases of the cell cycle. In the presynthetic phase, chromosomes are represented by one strand (chromatid); in the postsynthetic phase, they consist of two chromatids. During interphase, chromosomes occupy the entire volume of the nucleus, forming the so-called chromatin. The density of chromatin in different parts of the nucleus is not the same. Loose areas that are weakly stained with basic dyes are replaced by denser areas that are intensely stained.
The first are euchromatin: areas of dense chromatin contain heterochromatin or genetically inactivated parts of the chromosome.

Individually distinguishable chromosome bodies are formed at the time of cell division - mitosis or meiosis. In prophase of the first meiotic chromosome division. undergo a complex cycle of transformations associated with the conjugation of homologous chromosomes along the length with the formation of so-called bivalents and genetic recombination between them. During prophase of mitotic division, chromosomes appear as long intertwined strands. The formation of the chromosome “body” in the metaphase of cell division occurs by compaction of third-order structures in an as yet unknown way. The shortest length and characteristic morphological features of chromosomes can be observed precisely at the metaphase stage. Therefore, the description of the individual characteristics of individual chromosomes, as well as the entire chromosome set, always corresponds to their state in the metaphase of mitosis. Usually at this stage, chromosomes are longitudinally split structures consisting of two sister chromatids.
An obligatory element of the structure of chromium is the so-called primary constriction, where both chromatids narrow and remain united. Depending on the location of the centromere, chromosomes are distinguished as metacentric (the centromere is located in the middle), submetacentric (the centromere is displaced relative to the center) and acrocentric (the centromere is located close to the end of the chromosome). The ends of the chromosome are called telomeres.

The individualization of human chromosomes (and other organisms) is based on their ability to be stained with alternating light and dark transverse stripes along the length of the chromosome when using special staining methods. The number, position and width of such bands are specific to each chromosome. This ensures reliable identification of all human chromosomes in the normal chromosome set and makes it possible to decipher the origin of changes in chromosomes during cytogenetic examination of patients with various hereditary pathologies.

Maintaining the constancy of the number of chromosomes in the chromosome set and the structure of each individual chromosome. is an indispensable condition for the normal development of an individual in ontogenesis. However, during life, genomic and chromosomal mutations can occur in the body. Genomic mutations are a consequence of disruption of the mechanism of cell division and chromosome divergence. Polyploidy - an increase in the number of haploid sets of chromosomes more than diploid ones; Aneuploidy (change in the number of individual chromosomes) is possible as a result of the loss of one of two homologous chromosomes (monosomy) or, conversely, the appearance of extra chromosomes. - one, two or more (trisomy, tetrasomy, etc.). In somatic cells characterized by intensive functioning, the change in ploidy can be physiological (for example, physiological polyploidy in liver cells). However, aneuploidy in somatic cells is often observed during the development of tumors. Among children with hereditary chromosomal diseases, so-called aneuploids of individual autosomes and sex chromosomes predominate. Trisomy most often affects putosomes 8, 13, 18, 21 pairs and X chromosomes. As a result of trisomy of chromosome 21 pairs, Down's disease develops. An example of monosomy is Shereshevsky-Turner syndrome, caused by the loss of one of the X chromosomes. Aneuploidy, which occurs in the first divisions of the zygote, leads to the emergence of an organism with different numbers of X. of a given pair in different tissue cells (the phenomenon of mosaicism).

Genomic and chromosomal mutations play an important role in the evolution of biological species. A comparative study of chromosomes and chromosome sets made it possible to determine the degree of phylogenetic relationship between humans and apes, to model the set of chromosomes in their common ancestor, and to determine what structural rearrangements of chromosomes occurred during human evolution.

CHROMOSOME SET - a set of chromosomes characteristic of the cells of a given organism. There are two types of X. century: haploid - in mature germ cells and diploid - in somatic cells. During fertilization, two haploid X. are united, brought by male and female gametes, as a result of which a zygote with a diploid X. is formed. During meiosis, the diploid number of chromosomes is again reduced by half and gametes with a haploid X century are formed. If changes in the number of chromosomes are not multiples of the main number, X. c. called heteroplyid (for example, organisms that lack one chromosome in the diploid X. century are called monosomics).

Karyotype is a set of characteristics (number, size, shape, etc.) of a complete set of chromosomes inherent in the cells of a given biological species (species karyotype), a given organism (individual karyotype) or line (clone) of cells. A karyotype is sometimes also called a visual representation of the complete chromosome set (karyogram).

The term “karyotype” was introduced in 1924 by the Soviet cytologist G. A. Levitsky.

Determination of karyotype

The appearance of chromosomes changes significantly during the cell cycle: during interphase, chromosomes are localized in the nucleus, as a rule, despiralized and difficult to observe, therefore, to determine the karyotype, cells are used in one of the stages of their division - metaphase of mitosis.

Karyotype determination procedure

For the karyotype determination procedure, any population of dividing cells can be used. To determine the human karyotype, peripheral blood lymphocytes are usually used, the transition of which from the resting stage G0 to proliferation is provoked by the addition of the mitogen phytohemagglutinin. Bone marrow cells or a primary culture of skin fibroblasts can also be used to determine the karyotype. To increase the number of cells at the metaphase stage, colchicine or nocadazole is added to the cell culture shortly before fixation, which block the formation of microtubules, thereby preventing the divergence of chromatids to the poles of cell division and the completion of mitosis.

After fixation, preparations of metaphase chromosomes are stained and photographed; from the microphotographs, a so-called systematic karyotype is formed - a numbered set of pairs of homologous chromosomes, the images of the chromosomes are oriented vertically with short arms up, they are numbered in descending order of size, a pair of sex chromosomes is placed at the end of the set.

Historically, the first non-detailed karyotypes, which made it possible to classify according to chromosome morphology, were obtained using Romanovsky-Giemsa staining, but further detailing of the chromosome structure in karyotypes became possible with the advent of differential chromosome staining techniques. The most commonly used technique in medical genetics is the G-differential chromosome staining method.

Classical and spectral karyotypes

To obtain a classic karyotype, chromosomes are stained with various dyes or their mixtures: due to differences in the binding of the dye to different parts of the chromosomes, staining occurs unevenly and a characteristic banded structure is formed (a complex of transverse marks, English banding), reflecting the linear heterogeneity of the chromosome and specific for homologous pairs chromosomes and their sections (with the exception of polymorphic regions, various allelic variants of genes are localized). The first chromosome staining method to produce such highly detailed images was developed by the Swedish cytologist Kaspersson (Q-staining). Other dyes are also used, such techniques are collectively called differential chromosome staining:

Q-staining- Kaspersson staining with quinine mustard with examination under a fluorescent microscope. Most often used for the study of Y chromosomes (rapid determination of genetic sex, detection of translocations between the X and Y chromosomes or between the Y chromosome and autosomes, screening for mosaicism involving Y chromosomes)

G-staining- modified Romanovsky-Giemsa staining. The sensitivity is higher than that of Q-staining, therefore it is used as a standard method for cytogenetic analysis. Used to identify small aberrations and marker chromosomes (segmented differently than normal homologous chromosomes)

R-staining- acridine orange and similar dyes are used, and areas of chromosomes that are insensitive to G-staining are stained. Used to identify details of homologous G- or Q-negative regions of sister chromatids or homologous chromosomes.

C-staining- used to analyze centromeric regions of chromosomes containing constitutive heterochromatin and the variable distal part of the Y chromosome.

T-staining - used to analyze telomeric regions of chromosomes.

Recently, the so-called technique has been used. spectral karyotyping (fluorescence in situ hybridization, FISH), which consists of staining chromosomes with a set of fluorescent dyes that bind to specific regions of chromosomes. As a result of such staining, homologous pairs of chromosomes acquire identical spectral characteristics, which not only greatly facilitates the identification of such pairs, but also facilitates the detection of interchromosomal translocations, that is, movements of sections between chromosomes - translocated sections have a spectrum that differs from the spectrum of the rest of the chromosome.

Karyotype analysis

Comparison of complexes of transverse marks in classical karyotypy or areas with specific spectral characteristics makes it possible to identify both homologous chromosomes and their individual sections, which makes it possible to determine in detail chromosomal aberrations - intra- and interchromosomal rearrangements, accompanied by a violation of the order of chromosome fragments (deletions, duplications, inversions, translocation). Such an analysis is of great importance in medical practice, making it possible to diagnose a number of chromosomal diseases caused by both gross violations of karyotypes (violation of the number of chromosomes), and violation of the chromosomal structure or multiplicity of cellular karyotypes in the body (mosaicism).

Nomenclature

To systematize cytogenetic descriptions, the International System for Cytogenetic Nomenclature (ISCN) was developed, based on differential staining of chromosomes and allowing for a detailed description of individual chromosomes and their regions. The entry has the following format:

[chromosome number] [arm] [region number].[band number]

the long arm of a chromosome is designated by the letter q, the short arm by the letter p, and chromosomal aberrations are designated by additional symbols.

Thus, the 2nd band of the 15th section of the short arm of the 5th chromosome is written as 5p15.2.

For the karyotype, an ISCN 1995 entry is used, which has the following format:

[number of chromosomes], [sex chromosomes], [features].

To designate sex chromosomes in different species, different symbols (letters) are used, depending on the specifics of determining the sex of the taxon (different systems of sex chromosomes). Thus, in most mammals, the female karyotype is homogametic, and the male is heterogametic, respectively, the recording of the sex chromosomes of the female is XX, the male is XY. In birds, females are heterogametic, and males are homogametic, that is, the recording of the sex chromosomes of the female is ZW, and the male is ZZ.

Examples include the following karyotypes:

normal (specific) karyotype of a domestic cat: 38, XY

individual karyotype of a horse with an “extra” X chromosome (trisomy X chromosome): 65, XXX

individual karyotype of a domestic pig with a deletion (loss of a section) of the long arm (q) of chromosome 10: 38, XX, 10q-

individual karyotype of a man with translocation of 21 sections of the short (p) and long arms (q) of the 1st and 3rd chromosomes and deletion of the 22nd section of the long arm (q) of the 9th chromosome: 46, XY, t(1 ;3)(p21;q21), del(9)(q22)

Since normal karyotypes are species-specific, standard descriptions of karyotypes of various species of animals and plants, primarily domestic and laboratory animals and plants, are developed and maintained.

Medical cytogenetics is the study of human karyotype in normal and pathological conditions. This direction arose in 1956, when Tio and Levan improved the method of preparing preparations of metaphase chromosomes and for the first time established the modal number of chromosomes (2n=46) in a diploid set. In 1959, the chromosomal etiology of a number of diseases was deciphered - Down syndrome, Klinefelter syndrome, Shereshevsky-Turner syndrome and some other autosomal trisomy syndromes. Further development of medical cytogenetics in the late 1960s was due to the advent of methods for differential staining of metaphase chromosomes, making it possible to identify chromosomes and their individual regions. Differential staining methods did not always ensure the correct identification of breakpoints as a result of structural rearrangements of chromosomes. In 1976, Younis developed new methods for studying them at the prometaphase stage, which were called “high-resolution methods.”

The use of such methods made it possible to obtain chromosomes with different numbers of segments (from 550 to 850) and made it possible to identify disorders involving small sections of them (microrearrangements). Since the early 1980s. Human cytogenetics has entered a new stage of development: chromosomal analysis of molecular cytogenetic methods and fluorescence in situ hybridization (FISH - Fluorescence In Situ Hybridization) was introduced into practice. This method is widely used to detect more subtle structural abnormalities of chromosomes that are indistinguishable by differential staining. Currently, the use of various methods of chromosomal analysis makes it possible to successfully carry out pre- and postnatal diagnosis of chromosomal diseases.

Chromosomal diseases are a large group of clinically diverse conditions characterized by multiple congenital malformations, the etiology of which is associated with quantitative or structural changes in the karyotype.

Currently, almost 1000 chromosomal abnormalities are distinguished, of which more than 100 forms have a clinically defined picture and are called syndromes; their contribution to spontaneous abortions, neonatal mortality and morbidity is significant. The prevalence of chromosomal abnormalities among spontaneous abortions averages 50%, among newborns with severe multiple congenital malformations - 33%, stillborn and perinatal deaths with congenital malformations - 29%, premature babies with congenital malformations - 17%, newborns with congenital malformations - 10%, stillborn and perinatal deaths - 7%, premature - 2.5%, all newborns - 0.7%.

Most chromosomal diseases are sporadic, arising anew as a result of a genomic (chromosomal) mutation in the gamete of a healthy parent or in the first divisions of the zygote, and not inherited over generations, which is associated with the high mortality of patients in the pre-reproductive period.

The phenotypic basis of chromosomal diseases is disorders of early embryonic development. That is why pathological changes develop even in the prenatal period of development of the body and either cause the death of the embryo or fetus, or create the main clinical picture of the disease already in the newborn (with the exception of anomalies of sexual development, which form mainly during puberty). Early and multiple damage to body systems is characteristic of all forms of chromosomal diseases. These are craniofacial dysmorphia, congenital malformations of internal organs and body parts, slow intrauterine and postnatal growth and development, mental retardation, defects of the central nervous system, cardiovascular, respiratory, genitourinary, digestive and endocrine systems, as well as deviations in the hormonal , biochemical and immunological status. Each chromosomal syndrome is characterized by a complex of congenital malformations and developmental anomalies, which are inherent to some extent only in this type of chromosomal pathology. Clinical polymorphism of each chromosomal disease in its general form is determined by the genotype of the organism and environmental conditions. Variations in the manifestations of pathology can be very wide - from a lethal effect to minor developmental deviations. Despite the good study of the clinical manifestations and cytogenetics of chromosomal diseases, their pathogenesis, even in general terms, is not yet clear. A general scheme for the development of complex pathological processes caused by chromosomal abnormalities and leading to the appearance of complex phenotypes of chromosomal diseases has not been developed.

Main types of chromosomal abnormalities
All chromosomal diseases according to the type of mutations can be divided into two large groups: those caused by changes in the number of chromosomes while maintaining the structure of the latter (genomic mutations) and those caused by changes in the structure of the chromosome (chromosomal mutations). Genomic mutations arise due to nondisjunction or loss of chromosomes during gametogenesis or in the early stages of embryogenesis. Only three types of genomic mutations have been found in humans: tetraploidy, triploidy and aneuploidy. The incidence of triploid (Zn=69) and tetraploid (4n=92) mutations is very low, they are mainly found among spontaneously aborted embryos or fetuses and in stillborns. The life expectancy of newborns with such disorders is several days. Genomic mutations on individual chromosomes are numerous; they make up the bulk of chromosomal diseases. Moreover, of all the variants of aneuploidy, only trisomy on autosomes, polysomy on sex chromosomes (tri-, tetra- and pentasomy) are found, and among monosomies, only monosomy X is found.

Complete trisomies or monosomies are more difficult to tolerate by the body than partial ones; imbalances in large chromosomes occur in live births much less frequently than in small ones. Complete forms of chromosomal abnormalities cause significantly more serious abnormalities than mosaic ones. Autosomal monosomies are very rare among live births; they are mosaic forms with a large proportion of normal cells. The fact of the relatively low genetic value of heterochromatic regions of chromosomes has been proven. That is why complete trisomies in live births are observed in those autosomes that are rich in heterochromatin - 8, 9, 13, 14, 18, 21, 22 and X. This explains the good tolerance by patients of even a triple dose of Y-chromosome material and the almost complete loss of its long shoulder Complete monosomy on the X chromosome, compatible with postnatal life, leading to the development of Shereshevsky-Turner syndrome, as well as tetra- and pentasomy, are observed only on the X chromosome, which is heterochromatic.

Chromosomal mutations, or structural chromosomal rearrangements, are karyotype disorders, accompanied or not accompanied by an imbalance of genetic material within one or more chromosomes (intra- and interchromosomal rearrangements).

In the overwhelming majority of cases, structural chromosomal mutations are passed on to the offspring by one of the parents, whose karyotype contains a balanced chromosomal rearrangement. These include reciprocal (mutual) balanced translocation without loss of sections of the chromosomes involved in it. It, like inversion, does not cause pathological phenomena in the carrier. However, during the formation of gametes from carriers of balanced translocations and inversions, unbalanced gametes can be formed. Robertsonian translocation - a translocation between two acrocentric chromosomes with loss of their short arms - leads to the formation of one metacentric chromosome instead of two acrocentric ones. Carriers of this translocation are healthy because the loss of the short arms of two acrocentric chromosomes is compensated by the work of the same genes in the remaining 8 acrocentric chromosomes. During the maturation of germ cells, the random distribution (during cell division) of two rearranged chromosomes and their homologues leads to the appearance of several types of gametes, some of which are normal, others contain such a combination of chromosomes that, upon fertilization, give rise to a zygote with a balanced rearranged karyotype, while others produce a chromosomally unbalanced zygotes.

With an unbalanced chromosome set (deletions, duplications, insertions), the fetus develops severe clinical pathologies, usually in the form of a complex of congenital malformations. A lack of genetic material causes more serious developmental defects than an excess of it.

Much less often, structural aberrations arise de novo. The parents of a patient with a chromosomal disorder are usually karyotypically normal. Chromosomal disease in these cases occurs de novo as a result of transmission from one of the parents of a genomic or chromosomal mutation that occurs once in one of the gametes, or such a mutation occurs already in the zygote. This does not exclude the recurrence of a chromosomal disorder in children in a given family. There are families predisposed to repeated cases of chromosome nondisjunction. Mutations that arose de novo account for almost all cases of known complete trisomies and monosomies. The main mechanism for the occurrence of structural rearrangements of any type is a break in one or more chromosomes with the subsequent reunification of the resulting fragments.

Clinical indications for cytogenetic diagnosis
The cytogenetic research method occupies a leading place among laboratory diagnostic methods in medical genetic counseling and prenatal diagnosis. However, one should strictly adhere to objective
indications for referring patients for karyotype testing.

Main indications for prenatal diagnosis:
chromosomal abnormality in the previous child in the family;
stillborn baby with a chromosomal abnormality;
chromosomal rearrangements, chromosomal mosaicism or aneuploidy on sex chromosomes in parents;
results of a maternal blood serum test indicating an increased risk of a chromosomal abnormality in the fetus (risk group);
mother's age;
fetal anomalies detected by ultrasound examination;
suspicion of mosaicism in the fetus during a previous cytogenetic study;
suspected chromosomal instability syndrome.

Karyotype examination during postnatal diagnosis is recommended if the patient has:
primary or secondary amenorrhea or early menopause;
abnormal spermogram - azoospermia or severe oligospermia;
clinically significant deviations in growth (short, tall stature) and head size (micro-, macrocephaly);
abnormal genitalia;
abnormal phenotype or dysmorphia;
congenital malformations;
mental retardation or developmental disorders;
manifestations of deletion/microdeletion/duplication syndrome;
X-linked recessive disease in women;
clinical manifestations of chromosomal instability syndromes;
when monitoring after bone marrow transplantation.

Cytogenetic studies should be carried out in a married couple:
with chromosomal abnormalities or unusual chromosome variants in the fetus detected during prenatal diagnosis;
repeated miscarriages (3 or more); stillbirth, neonatal fetal death, inability to examine the affected fetus;
the child has a chromosomal abnormality or an unusual chromosomal variant;
infertility of unknown etiology.

The indication for cytogenetic research is the presence of the patient’s relatives:
chromosomal rearrangements;
mental retardation presumably of chromosomal origin;
reproductive losses, congenital malformations of the fetus or stillbirth of unknown origin.

Indications for research using the FISH method:
suspicion of microdeletion syndrome, for which molecular cytogenetic diagnostics are available (availability of appropriate DNA probes);
increased risk of microdeletion syndrome based on anamnestic data;
clinical signs suggesting mosaicism due to a certain chromosomal syndrome;
conditions after bone marrow transplantation, when the donor and recipient are of different sexes;
suspicion of a chromosomal abnormality during a standard cytogenetic study, when the FISH method may be useful for further 
clarification of the nature of the anomaly, or in situations where there are characteristic clinical manifestations;
the presence of a supernumerary marker chromosome;
suspicion of hidden chromosomal rearrangement.

The FISH method for analyzing metaphases is indicated:
with marker chromosomes;
additional material of unknown origin on the chromosome;
chromosomal rearrangements;
suspected loss of a chromosomal segment;
mosaicism.

The FISH method for analyzing interphase nuclei is indicated:
with numerical chromosomal abnormalities;
duplications;
divisions;
chromosome rearrangements;
determination of chromosomal sex;
gene amplification.

Cytogenetic research methods:
The study and description of the characteristic features of metaphase chromosomes are especially important for practical cytogenetics. Individual chromosomes within a group are recognized using differential staining techniques. These methods make it possible to detect the heterogeneity of the chromosome structure along the length, determined by the characteristics of the complex of the main molecular components of chromosomes - DNA and proteins. The problem of recognizing individual chromosomes in a karyotype is important for the development of cytogenetic diagnosis of chromosomal diseases in humans.

Cytogenetic research methods are divided into direct and indirect. Direct methods are used in cases where a quick result is needed and it is possible to obtain preparations of chromosomes of cells dividing in the body. Indirect methods include, as a mandatory step, more or less long-term cultivation of cells in artificial nutrient media. Methods that include short-term cultivation (from several hours to 2-3 days) occupy an intermediate position.

The main object of cytogenetic research using direct and indirect methods is the metaphase stage of mitosis and the various stages of meiosis. Metaphase of mitosis is the main subject of cytogenetic research, since it is at this stage that accurate identification of chromosomes and detection of their anomalies is possible. Chromosomes in meiosis are examined to detect certain types of rearrangements that, by their nature, are not detected in the metaphase of mitosis.

Biological material for cytogenetic studies. Processing of cell cultures. Preparation of chromosome preparations
Cells from any tissue available for biopsy can be used as material for obtaining human chromosomes and studying them. The most commonly used are peripheral blood, skin fibroblasts, bone marrow, amniotic fluid cells, and chorionic villous cells. Human peripheral blood lymphocytes are the most accessible for chromosome research.

Currently, almost all laboratories in the world use a method using whole peripheral blood to culture lymphocytes. Blood in the amount of 1-2 ml is taken in advance from the cubital vein into a sterile tube or bottle with heparin solution. Blood in a vial can be stored for 24-48 hours in the refrigerator at a temperature of 4-6 °C. Lymphocyte culture is carried out in a special box or in a workroom under a laminar flow hood under sterile conditions. Such conditions are mandatory to prevent the introduction of pathogenic flora into the blood culture. If there is suspicion of contamination of blood or other material, it is necessary to add antibiotics to the culture mixture. The vials with the culture mixture are incubated in a thermostat at a temperature of +37 °C for 72 hours (active cell growth and division is in progress). The main purpose of methodological techniques when processing cell cultures and preparing chromosome preparations from them is to obtain on the preparation a sufficient number of metaphase plates with such a spread of chromosomes that it is possible to estimate the length, shape and other morphological characteristics of each chromosome in the set.

The accumulation of cells in the metaphase of mitosis and the production of high-quality plates on the preparation occurs using a number of sequential procedures:
colchinization - exposure of cells to cytostatics colchicine or colcemid, blocking mitosis at the metaphase stage;
hypotonization of cultures;
fixation of cells with a mixture of methyl alcohol and acetic acid;
applying a cell suspension to a glass slide.

Colchinization of cell cultures is carried out 1.5-2 hours before the start of fixation. After colchicine is administered, the cell culture bottles continue to incubate in the thermostat. At the end of incubation, the culture mixture from each bottle is poured into clean centrifuge tubes and subjected to centrifugation. Then a hypotonic solution of potassium chloride, preheated to a temperature of +37 °C, is added to the cell sediment.

Hypotonization is carried out in a thermostat at a temperature of +37 °C for 15 minutes. A hypotonic KCI solution promotes better spread of chromosomes on a glass slide. After hypotonization, the cells are sedimented by centrifugation and subjected to fixation. Fixation is carried out with a mixture of methyl (or ethyl) alcohol and acetic acid.

The final stage is the preparation of chromosome preparations to obtain well-spread out metaphase plates while maintaining the integrity and completeness of the chromosome set in each of them. A cell suspension is applied to wet, cooled slides, after which the slides are dried at room temperature and labeled.

Methods for differential staining of chromosomes
Since 1971, methods have become widespread in cytogenetics that make it possible to differentially stain each chromosome of a set according to its length. The practical significance of these methods is that differential staining allows the identification of all human chromosomes due to the specific longitudinal staining pattern for each chromosome. Any paint consisting of a basic dye can be suitable for coloring, since the main coloring substrate of chromosomes is the DNA-protein complex. In the practice of cytogenetic research, the following methods are most widely used.

The G-staining method is the most common method due to its simplicity, reliability and availability of the necessary reagents. After staining, each pair of chromosomes acquires striations in length due to the alternation of differently colored heterochromatic (dark) and euchromatic (light) segments, which are usually referred to as G-segments. The C-staining method provides identification of only certain regions of chromosomes. These are regions of heterochromatin localized in the pericentromeric regions of the long arms of chromosomes 1, 9 and 16 and in the long arm of the Y chromosome, as well as in the short arms of acrocentric chromosomes. The R-method of coloring chromosome preparations shows a picture of differential segmentation inverse to the G-method. This method stains the distal segments of chromosomes well, which is very important when identifying small rearrangements involving the terminal sections. The Q-staining method provides differential fluorescent staining of individual chromosomes of the set, allows you to identify each pair of homologues, and also determine the presence of a Y chromosome in interphase nuclei by the glow of the Y-chromatin body.

Principles of chromosome analysis
An obligatory stage of the study is a visual analysis of chromosomes under a microscope using a thousandfold magnification (x1000) with x10 eyepieces and a x100 immersion objective. Assessment of the quality and suitability of chromosome preparations for research, as well as the selection of metaphase plates for analysis, is carried out at low magnification (x100). For the study, well-stained, complete metaphase plates with a good spread of chromosomes are selected. The researcher counts the total number of chromosomes and assesses the structure of each chromosome by comparing the striations of homologues, as well as comparing the observed pattern with cytogenetic maps (schemes) of chromosomes.

The use of computer image analysis systems significantly simplifies the task of a cytogeneticist, improves the quality of his work and provides the opportunity to quickly and easily document research results. To ensure high quality of work, it is recommended that two specialists participate in the cytogenetic study of each sample. The document confirming the study is the protocol, which indicates the coordinates of the examined cells, the number of chromosomes in each of them, the detected rearrangements, the karyotype formula and conclusion, as well as the patient’s surname, the date and number of the study, the surname and signature of the doctor (doctors) who conducted the study . Slides and chromosome images should be saved for later review.

BASIC RULES FOR THE DESCRIPTION OF CHROMOSOMAL ANOMALIES ACCORDING TO THE INTERNATIONAL SYSTEM OF CYTOGENETIC NOMENCLATURE
The karyotype formula must be recorded in accordance with the current version of the International System for human Cytogenetic Nomenclature. Below we consider aspects of the use of nomenclature that are most often encountered in clinical cytogenetic practice.

Number and morphology of chromosomes:
In a karyotype, chromosomes are divided into seven easily distinguishable groups (A-G) according to their size and centromere position. Autosomes are chromosomes 1 to 22, sex chromosomes are X and Y.
Group A (1-3) - large metacentric chromosomes that can be distinguished from each other by size and centromere position.
Group B (4-5) - large submetacentric chromosomes.
Group C (6-12, X) - metacentric and submetacentric chromosomes of medium size. The X chromosome is one of the largest chromosomes in this group.
Group D (13-15) - medium-sized acrocentric chromosomes with satellites. 
Group E (16-18) - relatively small metacentric and submetacentric chromosomes.
Group F (19-20) - small metacentric chromosomes.
Group G (21-22, Y) - small acrocentric chromosomes with satellites. The Y chromosome has no satellites.

Each chromosome consists of a continuous series of stripes, which are located along the length of the chromosome arms in strictly limited areas (sections). Chromosomal regions are specific to each chromosome and are essential for their identification. Bands and regions are numbered in the direction from centromere to telomere along the length of each arm. Regions are sections of a chromosome located between two adjacent bands. To designate the short and long arms of chromosomes, the following symbols are used: p - short arm and q - long arm. The centromere (sep) is designated by the symbol 10, the part of the centromere adjacent to the short arm is p10, and to the long arm is q10. The region closest to the centromere is designated by the number 1, the next region by the number 2, etc.

Four-digit symbolism is used to designate chromosomes:
1st character - chromosome number;
2nd character (p or q) - chromosome arm;
3rd character - number of the district (section);
The 4th character is the number of the lane within this area.

For example, entry 1p31 indicates chromosome 1, its short arm, region 3, band 1. If the band is divided into subbands, put a dot after the band designation, then write the number of each subband. Subbands, like stripes, are numbered in the direction from the centromere to the telomere. For example, in the 1p31 band there are three subbands: 1p31.1, 1p31.2 and 1p31.3, of which the 1p31.1 subband is proximal to the centromere, and the 1p31.3 subband is distal. If subbands are further subdivided into parts, they are numbered with numbers without punctuation. For example, subband 1р31.1 is divided into 1р31.11, 1р31.12, etc.

GENERAL PRINCIPLES FOR DESCRIPTION OF NORMAL AND ABNORMAL KARIOTYPE
In the description of the karyotype, the first point indicates the total number of chromosomes, including sex chromosomes. The first number is separated from the rest of the entry by a comma, then the sex chromosomes are written down. Autosomes are designated only in cases of abnormalities.

A normal human karyotype looks like this:
46,XX - normal karyotype of a woman;
46,XY is the normal karyotype of a man. 

In case of chromosomal anomalies, the anomalies of the sex chromosomes are recorded first, then the autosomal anomalies in ascending order of numbers and regardless of the type of anomaly. Each anomaly is separated by a comma. Letter designations are used to describe structurally rearranged chromosomes. The chromosome involved in the rearrangement is written in parentheses after the symbol indicating the type of rearrangement, for example: inv(2), del(4), r(18). If two or more chromosomes are involved in the rearrangement, a semicolon (;) is placed between the number designations of each of them.

Signs (+) or (-) are placed in front of a chromosome to indicate an abnormality, indicating an additional or missing chromosome (normal or abnormal), for example: +21,-7,+der(2). They are also used to indicate a decrease or increase in the length of a chromosome arm after the symbol (p or q); for this purpose, the above signs can only be used in the text, but not in the description of the karyotype, for example: 4p+, 5q-. When describing the sizes of heterochromatic segments, satellites and satellite filaments, the sign (+) (increase) or (-) (decrease) is placed immediately after the designation of the corresponding symbol, for example: 16qh+, 21ps+, 22pstk+. The multiplication sign (x) is used to describe multiple copies of rearranged chromosomes, but it cannot be used to describe multiple copies of normal chromosomes, for example: 46,XX,del(6)(q13q23)x2. To indicate alternative interpretations of anomalies, use the symbol (or), for example: 46,XX,del(8)(q21.1) or i(8)(p10).

Karyotypes of different clones are separated by a slash (/). Square brackets are placed after the description of the karyotype to indicate the absolute number of cells in a given clone. In order to indicate the reason for the emergence of different clones, the symbols mos (mosaicism - cell lines originated from the same zygote) and chi (chimera - cell lines originated from different zygotes) are used, which are given before the description of the karyotype. When listing karyotypes, the normal diploid clone is always listed last, for example: mos47,XY,+21/46,XY; mos47,XXY/46,XY.

If there are several anomalous clones, recording is carried out in order of increasing size: the first is the most frequently encountered, then descending. The last one is the normal clone, for example: mos45,X/47,XXX/46,XX. A similar notation is used in a karyotype that has two normal clones, for example: chi46,XX/46,XY. If two anomalous clones are present in the karyotype, one of which has a numerical anomaly, and the other has a structural rearrangement, then the clone with the numerical anomaly is recorded first. For example: 45,X/46,X,i(X)(q10).

When both clones have numerical anomalies, the clone with the autosome with the lower serial number is recorded first, for example: 47,XX,+8/47,XX,+21; the clone with sex chromosome abnormalities is always placed first, for example: 47,ХХХ/47,ХХ,+21.

The fact that the karyotype is haploid or polyploid will be obvious from the number of chromosomes and further designations, for example: 69,XXY. All altered chromosomes must be designated relative to the appropriate ploidy level, for example: 70,XXY,+21.

The maternal or paternal origin of an abnormal chromosome is indicated by the symbols mat and pat, respectively, after the described anomaly, for example: 46,XX,t(5;6)(q34;q23)mat,inv(14)(q12q31)pat; 46,XX,t(5;6)(q34;q23)mat,inv(14) (q12q31)mat. If it is known that the parents' chromosomes are normal in comparison with a given anomaly, it is considered as a new one and is designated by the symbol denovo (dn), for example: 46,XY,t(5;6)(q34;q23)mat,inv (14)( q12q31)dn.

Description of numerical chromosome abnormalities:
The sign (+) or (-) is used to indicate the loss or acquisition of an additional chromosome when describing numerical anomalies.
47,XX,+21 - karyotype with trisomy 21.
48,XX,+13,+21 - karyotype with trisomy 13 and trisomy 21.
45,XX,-22 - karyotype with monosomy 22.
46,XX,+8,-21 - karyotype with trisomy 8 and monosomy 21.
An exception to this rule are constitutional abnormalities of the sex chromosomes, which are written without using the signs (+) and (-).
45,X - karyotype with one X chromosome (Shereshevsky-Turner syndrome).
47,XXY - karyotype with two X chromosomes and one Y chromosome (Klinefelter syndrome).
47,XXX - karyotype with three X chromosomes.
47,XYY - karyotype with one X chromosome and two Y chromosomes.
48,XXXY is a karyotype with three X chromosomes and one Y chromosome.

Description of structural abnormalities of chromosomes
In describing structural changes, both brief and detailed recording systems are used. When using the short system, only the type of chromosomal rearrangement and breakpoints are indicated. Write down the type of chromosomal abnormality, the chromosome involved in this abnormality, and the breakpoints in parentheses. The short system does not allow an unambiguous description of complex chromosomal rearrangements, which are sometimes detected when analyzing tumor karyotypes.

Brief system for designating structural adjustments
If both arms are involved in a rearrangement resulting from two breaks occurring in one chromosome, the breakpoint in the short arm is recorded before the breakpoint in the long arm: 46,XX,inv(2)(p21q31). When two breakpoints are on the same chromosome arm, the breakpoint proximal to the centromere is indicated first: 46,XX,inv(2)(p13p23). In the case when two chromosomes are involved in the rearrangement, either the chromosome with a lower serial number or the sex chromosome is indicated first: 46,XY,t(12;16)(q13;p11.1); 46,X,t(X;18) (p11.11;q11.11).

The exception to the rule is rearrangements with three breakpoints, when a fragment of one chromosome is inserted into a region of another chromosome. In this case, the recipient chromosome is written first, and the donor chromosome last, even if it is a sex chromosome or a chromosome with a lower serial number: 46,X,ins(5;X)(p14;q21q25); 46,XY,ins(5;2)(p14;q22q32). If the rearrangement affects one chromosome, the breakpoints in the segment where the insertion was formed are indicated first. In the case of direct insertion, the break point of the inserted fragment proximal to the centromere is recorded first, and then the distal break point. With an inverted insertion, the opposite is true.

To indicate translocations in which three different chromosomes are involved, the sex chromosome or the chromosome with a lower serial number is indicated first, then the chromosome that received a fragment from the first chromosome, and, finally, the chromosome that donated the fragment to the first chromosome. 46,XX,t(9;22;17) (q34;q11.2;q22) - a fragment of chromosome 9, corresponding to the distal region 9q34, transferred to chromosome 22, to segment 22q11.2, a fragment of chromosome 22, corresponding to the distal region 22q11 .2 is transferred to chromosome 17, in segment 17q22, and the fragment of chromosome 17, corresponding to the distal region of 17q22, is transferred to chromosome 9, in segment 9q34. 

Detailed system for designating structural changes. In accordance with a detailed notation system, structural rearrangements of chromosomes are determined by the composition of the bands in them. All notations used in the short system are retained in the detailed system. However, in a detailed system, a detailed description of the composition of bands in rearranged chromosomes is given using additional symbols. A colon (:) indicates a break point, and a double colon (::) indicates a break followed by a reunion. The arrow (->) indicates the direction of transfer of chromosome fragments. The ends of chromosome arms are designated by the symbol ter (terminal), pter or qter indicating the end of the short or long arm, respectively. The symbol sep is used to indicate the centromere.

Types of chromosomal rearrangements
Additional material of unknown origin. The symbol add (from Latin additio - addition) is used to indicate additional material of unknown origin that has been added to a chromosomal region or band. Additional material attached to the terminal region will cause an increase in the length of the chromosome arm. When describing chromosomes with additional material of unknown origin in both arms, the symbol der is placed before the chromosome number. If unknown extra material is inserted into a chromosome arm, the symbols ins and (?) are used for description.

Deletions. The del symbol is used to indicate terminal and interstitial deletions:
46,XX,del(5)(q13)
46,XX,del (5) (pter->q13:)
The sign (:) means that the break occurred in the 5q13 band, as a result, chromosome 5 consists of a short arm and part of the long arm, located between the centromere and the 5q13 segment.
46,XX,del(5)(q13q33)
46,XX,del(5)(pter->q13::q33->qter)
The sign (::) means a break and rejoining of bands 5ql3 and 5q33 of the long arm of chromosome 5. The chromosome segment between these bands is deleted.

Derivative, or derivative, chromosomes (der) are chromosomes that arise as a result of rearrangements affecting two or more chromosomes, as well as as a result of multiple rearrangements within one chromosome. The number of the derivative chromosome corresponds to the number of the intact chromosome, which has the same centromere as the derivative chromosome:
46,XY,der(9)del(9)(p12)del(9)(q31)
46,XY,der(9) (:р12->q31:)
Derivative chromosome 9 is the result of two terminal deletions occurring in the short and long arms, with breakpoints at bands 9p12 and 9q31, respectively.
46,XX,der (5)add(5)(p15.1)del(5)(q13)
46,XX,der(5)(?::p15.1-»q13:)
Derived chromosome 5 with additional material of unknown origin attached to band 5p15.1 and a terminal deletion of the long arm distal to band 5q13.

Dicentric chromosomes. The symbol die is used to describe dicentric chromosomes. A dicentric chromosome replaces one or two normal chromosomes. Thus, there is no need to indicate missing normal chromosomes. 
45,XX,dic(13;13)(q14;q32)
45,XX,dic(13;13)(13pter->13ql4::13q32-»13pter)
The breakage and reunion occurred in bands 13ql4 and 13q32 on two homologous chromosomes 13, resulting in a dicentric chromosome.

Duplications. Duplications are indicated by the symbol dup; they can be direct or inverted.
46,XX,dup(1)(q22q25)
46,XX,dup(1)(pter->q25::q22->qter)
Direct duplication of the segment between bands lq22 and lq25.
46,XY,dup(1)(q25q22)
46,XY,dup(1) (pter->q25::q25->q22::q25->qter) or (pter->q22::q25-»q22::q22->qter)
Inverted duplication of the segment between bands lq22 and lq25. It should be noted that only a detailed system makes it possible to describe inverted duplication.

Inversions. The symbol inv is used to describe para- and pericentric inversions.
46,XX,inv(3)(q21q26.2)
46,XX,inv(3)(pter->q21::q26.2->q21::q26.2->qter)
Paracentric inversion, in which the break and rejoining occurred in bands 3q21 and 3q26.2 of the long arm of chromosome 3.
46,XY,inv(3)(p13q21)
46,XY,inv(3)(pter-»pl3::q21->p13::q21->qter)
Pericentric inversion, in which the break and rejoining occurred between the short arm band 3p13 and the long arm band 3q21 of chromosome 3. The region between these bands, including the centromere, is inverted 180°.

Insertions. The symbol ins is used to indicate direct or inverted insertion. An insertion is considered direct when the proximal end of the insertion region is in a proximal position relative to its second end. With an inverted insertion, the proximal end of the insertion region is in a distal position. The type of insertion (direct or inverted) can also be indicated by the symbols dir and inv, respectively.
46,XX,ins(2)(pl3q21q31)
46,XX,ins(2)(pter->p13::q31->q21::pl3-»q21::q31-qter)
A direct insertion, i.e. dir ins(2) (p13q21q31), occurred between segments 2q21 and 2q31 of the long arm and segment 2p13 of the short arm of chromosome 2. The region of the long arm chromosome between segments 2q21 and 2q31 is inserted into the short arm in the region of segment 2p13. In the new position, segment 2q21 remains closer to the centromere than segment 2q31.
46,XY,ins(2) (pl3q31q21)
46,XY,ins(2)(pterH>pl3::q21->q31::pl3->q21::q31-»qter)
In this case, the inserted section is inverted, i.e. inv ins(2)(p13q31q21). In the insert, segment 2q21 is further from the centromere than segment 2q31. Thus, the location of the segments relative to the centromere has changed.

Isochromosomes. The symbol i is used to describe isochromosomes, which are chromosomes consisting of two identical arms. Breakpoints in isochromosomes are localized in the centromeric regions p10 and q10.
46,XX,i(17)(q10)
46,XX,i(17)(qter-»q10::q10 ->qter) 
The isochromosome along the long arm of chromosome 17 and the breakpoint are designated in the region of 17q10. The karyotype contains one normal chromosome and one rearranged chromosome 17.
46,X,i(X)(q10)
46,X,i(X) (qter-»q10::q10->qter)
One normal X chromosome and an X isochromosome on the long arm.

Fragile sites (fragile sites) may appear as normal polymorphisms or may be associated with hereditary diseases or phenotypic abnormalities.
46,X,fra(X)(q27.3)
A fragile region in the Xq27.3 subband of one of the X chromosomes in the female karyotype.
46,Y,fra(X)(q27.3)
A fragile region in the Xq27.3 subband of the X chromosome in the male karyotype.

A marker chromosome (tag) is a structurally altered chromosome, no part of which can be identified. If any part of an abnormal chromosome is identified, it is described as a derived chromosome (der). When describing a karyotype, a (+) sign is placed before the mar symbol.
47,XX,+mar
One additional marker chromosome.
48,X,t(X;18)(p11.2;q11.2)+2mar
Two marker chromosomes in addition to the t(X;18) translocation.

Ring chromosomes are designated by the symbol r and can consist of one or more chromosomes.
46,XX,r(7)(p22q36)
46,XX,r(7) (::р22->q36::)
Breakage and rejoining occurred in segments 7p22 and 7q36, with loss of chromosome regions distal to these breakpoints.
If the centromere of a ring chromosome is unknown, but the chromosome segments contained in the ring are known, the ring chromosomes are defined as derivatives (der).
46,XX,der(1)r(1;3)(p36.1q23;q21q27)
46,XX,der(1)(::lp36.1->1q23::3q21->3q27::)

Translocations. Reciprocal translocations
To describe translocations (t), the same principles and rules are used as to describe other chromosomal rearrangements. To distinguish homologous chromosomes, one of the homologues may be underlined with a single underscore (_).
46,XY,t(2;5)(q21;q31)
46,XY,t(2;5)(2pter2q21::5q31->5qter;5pter 5q31::2q21->2qter)
The break and reunion occurred in segments 2q21 and 5q31. The chromosomes exchanged regions distal to these segments. The chromosome with the lower serial number is indicated first.
46,X,t(X;13)(q27;ql2)
46,X,t(X;13)(Xpter->Xq27::13ql2->13qter;13pter->3q 12::Xq27->Xqter)
Breakdown and reunion occurred in segments Xq27 and 13q12. The segments distal to these areas were swapped. Since the sex chromosome is involved in the translocation, it is recorded first. Note that the correct notation is 46,X,t(X;13), not 46,XX,t(X;13).
46,t(X;Y) (q22;q1, 1.2) 
46,t(X;Y)(Xpter->Xq22::Yq11.2->Yqter;Ypter->Yq11.2::Xq22->Xqter)
Reciprocal translocation between the X and Y chromosomes with breakpoints Xq22 and Yq11.2.
Translocations involving entire chromosome arms can be recorded indicating breakpoints in the centromeric regions of p10 and q10. In balanced translocations, the breakpoint in the sex chromosome or in the chromosome with a lower serial number is designated p10.
46,XY,t(4;3)(p10;q10)
46,XY,t(1;3)(lpteMlpl0::3ql0->3qter;3pter->3p40::4q40->4qter)
Reciprocal translocation of entire chromosome arms, in which the short arms of chromosome 1 joined the centromere with the long arms of chromosome 3, and the long arms of chromosome 1 joined the short arms of chromosome 3.
In unbalanced translocations of entire chromosome arms, the rearranged chromosome is designated as a derivative (der) and replaces two normal chromosomes.
45,XX,der(1;3) (p10;q10)
45,XX,der(1;3)(1pter->1p10::3q10->3qter)

A derived chromosome consisting of the short arm of chromosome 1 and the long arm of chromosome 3. The missing chromosomes 1 and 3 are not labeled because they are replaced by the derived chromosome. The karyotype thus contains one normal chromosome 1, one normal chromosome 3 and the derivative chromosome der(l;3).

Robertsonian translocations
This is a special type of translocation that occurs as a result of the centric fusion of the long arms of acrocentric chromosomes 13-15 and 21-22 with the simultaneous loss of the short arms of these chromosomes. The principles for describing unbalanced translocations involving entire arms also apply to describing Robertsonian translocations using the symbol (der). The symbol rob may also be used to describe these translocations, but it should not be used to describe acquired anomalies. The breakpoints of the chromosomes involved in the translocation are indicated in the q10 regions.
45,XX,der(13;21) (q10;q10)
45,XX,rob(13;21) (q10;q10)

The breakage and reunion occurred in segments 13q10 and 21q10 of the centromeric regions of chromosomes 13 and 21. The derived chromosome replaced one chromosome 13 and one chromosome 21. There is no need to indicate the missing chromosomes. The karyotype contains one normal chromosome 13, one normal chromosome 21 and der (13;21). The imbalance occurs due to the loss of the short arms of chromosomes 13 and 21.

Heredity and variability in living nature exist thanks to chromosomes, genes, (DNA). It is stored and transmitted as a chain of nucleotides as part of DNA. What role do genes play in this phenomenon? What is a chromosome from the point of view of transmission of hereditary characteristics? Answers to questions like these provide insight into coding principles and genetic diversity on our planet. It largely depends on how many chromosomes are included in the set and on the recombination of these structures.

From the history of the discovery of “particles of heredity”

Studying plant and animal cells under a microscope, many botanists and zoologists in the middle of the 19th century drew attention to the thinnest threads and the smallest ring-shaped structures in the nucleus. More often than others, the German anatomist Walter Flemming is called the discoverer of chromosomes. It was he who used aniline dyes to treat nuclear structures. Flemming called the discovered substance “chromatin” for its ability to stain. The term “chromosomes” was introduced into scientific use in 1888 by Heinrich Waldeyer.

At the same time as Flemming, the Belgian Eduard van Beneden was looking for an answer to the question of what a chromosome is. A little earlier, German biologists Theodor Boveri and Eduard Strassburger conducted a series of experiments proving the individuality of chromosomes and the constancy of their number in different species of living organisms.

Prerequisites for the chromosomal theory of heredity

American researcher Walter Sutton found out how many chromosomes are contained in the cell nucleus. The scientist considered these structures to be carriers of units of heredity, characteristics of the organism. Sutton discovered that chromosomes consist of genes through which properties and functions are passed on to offspring from their parents. The geneticist in his publications gave descriptions of chromosome pairs and their movement during the division of the cell nucleus.

Regardless of his American colleague, work in the same direction was carried out by Theodore Boveri. Both researchers in their works studied the issues of transmission of hereditary characteristics and formulated the main provisions on the role of chromosomes (1902-1903). Further development of the Boveri-Sutton theory took place in the laboratory of Nobel laureate Thomas Morgan. The outstanding American biologist and his assistants established a number of patterns of gene placement on the chromosome and developed a cytological basis that explains the mechanism of the laws of Gregor Mendel, the founding father of genetics.

Chromosomes in a cell

The study of the structure of chromosomes began after their discovery and description in the 19th century. These bodies and filaments are found in prokaryotic organisms (non-nuclear) and eukaryotic cells (in nuclei). Study under a microscope made it possible to establish what a chromosome is from a morphological point of view. It is a mobile filamentous body that is visible during certain phases of the cell cycle. In interphase, the entire volume of the nucleus is occupied by chromatin. During other periods, chromosomes are distinguishable in the form of one or two chromatids.

These formations are better visible during cell division - mitosis or meiosis. More often, large chromosomes of a linear structure can be observed. In prokaryotes they are smaller, although there are exceptions. Cells often contain more than one type of chromosome, for example mitochondria and chloroplasts have their own small “particles of inheritance”.

Chromosome shapes

Each chromosome has an individual structure and differs from others in its coloring features. When studying morphology, it is important to determine the position of the centromere, the length and placement of the arms relative to the constriction. The set of chromosomes usually includes the following forms:

• metacentric, or equal arms, which are characterized by a median location of the centromere;
• submetacentric, or unequal arms (the constriction is shifted towards one of the telomeres);
• acrocentric, or rod-shaped, in which the centromere is located almost at the end of the chromosome;
• dotted with a difficult-to-define shape.

Functions of chromosomes

Chromosomes consist of genes - functional units of heredity. Telomeres are the ends of chromosome arms. These specialized elements serve to protect against damage and prevent fragments from sticking together. The centromere performs its tasks during chromosome doubling. It has a kinetochore, and it is to this that the spindle structures are attached. Each pair of chromosomes is individual in the location of the centromere. The spindle threads work in such a way that one chromosome at a time goes to the daughter cells, not both. Uniform doubling during division is provided by the origins of replication. Duplication of each chromosome begins simultaneously at several such points, which significantly speeds up the entire division process.

Role of DNA and RNA

It was possible to find out what a chromosome is and what function this nuclear structure performs after studying its biochemical composition and properties. In eukaryotic cells, nuclear chromosomes are formed by a condensed substance - chromatin. According to the analysis, it contains high-molecular organic substances:

Nucleic acids are directly involved in the biosynthesis of amino acids and proteins and ensure the transmission of hereditary characteristics from generation to generation. DNA is contained in the nucleus of a eukaryotic cell, RNA is concentrated in the cytoplasm.

Genes

X-ray diffraction analysis showed that DNA forms a double helix, the chains of which consist of nucleotides. They represent the carbohydrate deoxyribose, a phosphate group, and one of four nitrogenous bases:

Regions of helical deoxyribonucleoprotein strands are genes that carry encoded information about the sequence of amino acids in proteins or RNA. During reproduction, hereditary characteristics from parents are transmitted to offspring in the form of gene alleles. They determine the functioning, growth and development of a particular organism. According to a number of researchers, those sections of DNA that do not encode polypeptides perform regulatory functions. The human genome can contain up to 30 thousand genes.

Set of chromosomes

The total number of chromosomes and their features are a characteristic feature of the species. In the Drosophila fly their number is 8, in primates - 48, in humans - 46. This number is constant for the cells of organisms that belong to the same species. For all eukaryotes there is the concept of “diploid chromosomes”. This is a complete set, or 2n, as opposed to haploid - half the number (n).

Chromosomes in one pair are homologous, identical in shape, structure, location of centromeres and other elements. Homologues have their own characteristic features that distinguish them from other chromosomes in the set. Staining with basic dyes allows you to examine and study the distinctive features of each pair. is present in the somatic ones - in the reproductive ones (the so-called gametes). In mammals and other living organisms with a heterogametic male sex, two types of sex chromosomes are formed: the X chromosome and the Y. Males have a set of XY, females have a set of XX.

Human chromosome set

The cells of the human body contain 46 chromosomes. All of them are combined into 23 pairs that make up the set. There are two types of chromosomes: autosomes and sex chromosomes. The first form 22 pairs - common for women and men. What differs from them is the 23rd pair - sex chromosomes, which are non-homologous in the cells of the male body.

Genetic traits are associated with gender. They are transmitted by a Y and an X chromosome in men and two X chromosomes in women. Autosomes contain the rest of the information about hereditary traits. There are techniques that allow you to individualize all 23 pairs. They are clearly distinguishable in the drawings when painted in a certain color. It is noticeable that the 22nd chromosome in the human genome is the smallest. Its DNA, when stretched, is 1.5 cm long and has 48 million nitrogen base pairs. Special histone proteins from the composition of chromatin perform compression, after which the thread takes up thousands of times less space in the cell nucleus. Under an electron microscope, the histones in the interphase core resemble beads strung on a strand of DNA.

Genetic diseases

There are more than 3 thousand hereditary diseases of various types caused by damage and abnormalities in chromosomes. These include Down syndrome. A child with such a genetic disease is characterized by delays in mental and physical development. With cystic fibrosis, a malfunction occurs in the functions of the exocrine glands. Violation leads to problems with sweating, secretion and accumulation of mucus in the body. It makes it difficult for the lungs to function and can lead to suffocation and death.

Color vision impairment - color blindness - insensitivity to certain parts of the color spectrum. Hemophilia leads to weakened blood clotting. Lactose intolerance prevents the human body from digesting milk sugar. In family planning offices you can find out about your predisposition to a particular genetic disease. In large medical centers it is possible to undergo appropriate examination and treatment.

Gene therapy is a direction of modern medicine, identifying the genetic cause of hereditary diseases and eliminating it. Using the latest methods, normal genes are introduced into pathological cells instead of damaged ones. In this case, doctors relieve the patient not from the symptoms, but from the causes that caused the disease. Only correction of somatic cells is carried out; gene therapy methods are not yet applied en masse to germ cells.