5.2. Chromosomal mutations

Chromosomal mutations are divided into two categories: 1) mutations associated with changes in the number of chromosomes in the karyotype (sometimes they are also called numerical aberrations or genomic mutations); 2) mutations consisting in changes in the structure of individual chromosomes (structural aberrations).

Changes in the number of chromosomes. They can be expressed in addition to the initial diploid set of chromosomes (2n) of one or more haploid sets (n), which leads to the emergence of polyploidy (triploidy, 3n, tetraploidy, 4n, etc.). It is also possible to add or lose one or more chromosomes, resulting in aneuploidy (heteroploidy). If aneuploidy is associated with the loss of one chromosome (formula 2n-1), then it is customary to speak of monosomy; loss of a pair of homologous chromosomes (2n-2) leads to nullisomy; when one chromosome (2n + 1) is added to the diploid set, trisomy occurs. In cases where there is an increase in the set by two and more chromosomes (but less than the haploid number), the term "polysemy" is used.

Polyploidy is very common in some plant groups. Obtaining polyploid varieties cultivated plants is important task breeding practice, since with an increase in ploidy, the economic value of such plants increases (leaves, stems, seeds, fruits become larger). On the other hand, polyploidy is quite rare in dioecious animals, since in this case the balance between sex chromosomes and autosomes is often disturbed, which leads to infertility of individuals or to lethality (death of the organism). In mammals and humans, the resulting polyploids, as a rule, die at the early stages of ontogeny.

Aneuploidy is observed in many species of organisms, especially in plants. Trisomy of some agricultural plants also have a certain practical value, while monosomy and nullisomy often lead to the non-viability of the individual. Human aneuploidies are the cause of severe chromosomal pathology, which manifests itself in serious violations development of the individual, his disability, often ending in the early death of the organism at a particular stage of ontogenesis (lethal outcome). Human chromosomal diseases will be considered in more detail in subsection. 7.2.

The causes of polyploidy and aneuploidy are associated with violations of the divergence of the diploid complex of chromosomes (or chromosomes of individual pairs) of parent cells into daughter cells during meiosis or mitosis. So, for example, if a person during oogenesis has a nondisjunction of one pair of autosomes of the mother cell with a normal karyotype (46, XX), then the formation of eggs with mutant karyotypes 24 ,X and 22 X. Therefore, when such eggs are fertilized by normal spermatozoa (23,X or 23,X), zygotes (individuals) with trisomy may appear. (47,XX either 47 ,XY) and with monosomy (45,XX or 45,XY) for the corresponding autosome. On fig. 5.1 is given general scheme possible violations oogenesis at the stage of reproduction of primary diploid cells (during the mitotic division of oogonia) or during the maturation of gametes (during the division of meiosis), leading to the emergence of triploid zygotes (see Fig. 3.4). Similar effects will be observed with appropriate disorders of spermatogenesis.

If the above disorders affect mitotically dividing cells at the early stages of embryonic development (embryogenesis), then individuals appear with signs of mosaicism (mosaic), i.e. having both normal (diploid) cells and aneuploid (or polyploid) cells.

Currently, various agents are known, for example, high or low temperatures, some chemical substances, called "mitotic poisons" (colchicine, heteroauxin, acenaphthol, etc.), which violate normal work cell division apparatus in plants and animals, preventing

normal completion of the process of chromosome segregation in anaphase and telophase. With these agents, experimental conditions receive polyploid and aneuploid cells of different eukaryotes.

Changes in the structure of chromosomes (structural aberrations). Structural aberrations are intrachromosomal or interchromosomal rearrangements that occur when chromosomes break under the influence of mutagens. environment or as a result of violations in the mechanism of crossing over, leading to an incorrect (unequal) genetic exchange between homologous chromosomes after enzymatic "cutting" of their conjugating sites.

Intrachromosomal rearrangements include deletions (deficiencies), i.e. losses individual sections chromosomes, duplications (duplications) associated with the doubling of certain sections, as well as inversions and non-reciprocal translocations (transpositions) that change the order of genes in the chromosome (in the linkage group). An example of interchromosomal rearrangements are reciprocal translocations (Fig. 5.2).

Deletions and duplications can change the number of individual genes in the genotype of an individual, which leads to an imbalance in their regulatory relationships and corresponding phenotypic manifestations. Large deletions are usually lethal in the homozygous state, while very small deletions are most often not. direct cause death of homozygotes.

Inversion occurs as a result of a complete rupture of the two edges of the chromosome region, followed by a turn of this region by 180° and the reunion of the broken ends. Depending on whether the centromere is included or not included in the inverted region of the chromosome, inversions are divided into pericentric and paracentric (see Fig. 5.2). The resulting permutations in the location of the genes of an individual chromosome (rearrangements of the linkage group) can also be accompanied by impaired expression of the corresponding genes.

Rearrangements that change the order and (or) content of gene loci in linkage groups also occur in the case of translocations. The most common are reciprocal translocations, in which there is a mutual exchange of previously broken sections between two non-homologous chromosomes. In the case of non-reciprocal translocation, the damaged area moves (transposition) within the same chromosome or into the chromosome of another pair, but without mutual (reciprocal) exchange (see Fig. 5.2).

explanation of the mechanism of such mutations. These rearrangements consist in the centric fusion of two nonhomologous chromosomes into one or in the division of one chromosome into two as a result of its break in the centromere region. Therefore, such rearrangements can lead to a change in the number of chromosomes in the karyotype without affecting total genetic material in a cell. It is believed that Robertsonian translocations are one of the factors in the evolution of karyotypes in different types eukaryotic organisms.

As noted earlier, in addition to errors in the recombination system, structural aberrations are usually caused by chromosome breaks that occur under the action of ionizing radiation, some chemicals, viruses and other agents.

The results of an experimental study of chemical mutagens indicate that heterochromatic regions of chromosomes are the most sensitive to their effects (most often breaks occur in the centromere region). In the case of ionizing radiation, this regularity is not observed.

Basic terms and concepts: aberration; aneuploidy (heteroploidy); deletion (lack); duplication (duplication); mortality; "mitotic poisons"; monosomy; non-reciprocal translocation; nullisomy; paracentric inversion; pericentric inversion; polyploidy; polysemy; reciprocal translocation; Robertsonian translocation; transposition; trisomy; chromosomal mutation.

Chromosomal mutations (also called rearrangements, aberrations) are caused by wrong division cells and change the structure of the chromosome itself. Most often this happens spontaneously and unpredictably under the influence external factors. Let's talk about the types of chromosomal mutations in genes and their causes. We will tell you what a chromosomal mutation is and what consequences arise for the body as a result of such changes.

Chromosomal mutation- This is a spontaneously occurring anomaly with a single chromosome or with the participation of several of them. The changes that have taken place are:

• inside a single chromosome, they are called intrachromosomal;
• interchromosomal, when individual chromosomes exchange certain fragments with each other.

What can happen to the carrier of information in the first case? As a result of the loss of a chromosomal region, a violation of embryogenesis occurs and various anomalies occur, leading to mental underdevelopment of the child or physical deformities (heart defects, a violation of the structure of the larynx and other organs). If a chromosome break occurs, after which the torn fragment is built into its place, but already turned over by 180 ° - they speak of inversion. The order of the genes changes. Another intrachromosomal mutation is a duplication. In its process, a portion of the chromosome is doubled or it is duplicated several times, which leads to multiple defects in the mental and physical development.

If two chromosomes exchange fragments, the phenomenon is called “reciprocal translocation”. If a fragment of one chromosome is inserted into another, this is called a “non-reciprocal translocation”. “Centric fusion” is the connection of a pair of chromosomes in the region of their centromeres with the loss of neighboring regions. With a mutation in the form of a transverse gap adjacent chromosomes are called isochromosomes. Such changes do not external manifestations in the born offspring, but makes it a carrier of abnormal chromosomes, which may affect the occurrence of abnormalities in future generations. All types of chromosomal mutation are fixed in the genes and are inherited.

Main Causes of Chromosome Mutations

Exact Causes of Chromosomal Mutations cannot be determined in any particular case. In general, DNA mutations are a tool natural selection and a sine qua non for evolution. They may have a positive neutral or negative meaning and are inherited. All mutagens that can lead to changes in chromosomes are usually divided into 3 types:

• biological (bacteria, viruses);
• chemical (salts heavy metals, phenols, alcohols and other chemicals);
• physical (radioactive and ultraviolet radiation, too low and high temperatures, electromagnetic field).

Spontaneous chromosomal rearrangements can also occur, without the influence of aggravating factors, but such cases are extremely rare. This happens under the influence of internal and external conditions(the so-called mutational pressure of the environment). Such randomness leads to a change in genes and their new distribution in the genome. The further viability of organisms with the resulting changes is determined by the ability to adapt to survival, which is part of natural selection. For a person, for example, mutation processes often become a source of various hereditary diseases, sometimes incompatible with life.

What is the difference between gene, genomic and chromosomal mutations

Mutations in chromosomes, genes, and the genome are often associated with each other. A mutation is called a gene. occurring inside the gene, chromosomal - inside the chromosome. Mutations that change the number of chromosomes are called genomic mutations.

These changes are combined into general concept“chromosomal abnormalities”, they have general classification, which subdivides them into aneuploidy and polyploidy.

In total, about a thousand chromosomal and genomic anomalies are known to science, including various syndromes (about 300 species). These are chromosomal diseases. (a prime example- Down syndrome), and intrauterine pathologies leading to miscarriages, and somatic diseases.

Chromosomal diseases

Their manifestation is spoken of when severe congenital genetically determined diseases are detected, manifested by congenital malformations. Such diseases testify to the most extensive changes that have occurred in DNA.

Failure can occur at any stage, even at the moment of conception, with the fusion of normal parental cells. Scientists have not yet been able to influence this mechanism and prevent it. This question has not been fully studied.

For humans, chromosomal mutations are more common negative character, which manifests itself in the occurrence of miscarriages, stillbirths, the manifestation of deformities and deviations in the intellect, the appearance of genetically determined tumors. All such diseases conditionally divided into 2 groups:

Can chromosomal abnormalities be cured or prevented?

In the future, science sets the task of learning how to interfere with the structure of cells and change human DNA if necessary, but at the current moment this is impossible. As such, there is no treatment for chromosomal diseases; only methods of perinatal diagnosis (prenatal examination of the fetus) have been developed. Using this method, it is possible to identify Down and Edwards syndromes, as well as congenital malformations of the organs of an unborn baby.

According to the examination, the doctor, together with the parents, decides on the extension or termination of current pregnancy. If the pathology suggests the possibility of intervention, the fetus can be rehabilitated even at the stage of intrauterine development, including an operation that eliminates the defect.

Future parents at the stage of pregnancy planning can visit a genetic consultation, which exists in almost every city. This is especially necessary if there are relatives in the family of one or both with severe hereditary diseases. The geneticist will compile their pedigree and recommend a study - a complete set of chromosomes.

Doctors believe that such a gene analysis is necessary for every couple planning the appearance of a baby. This is a low-cost, universal and fast method that allows you to determine the presence of most chromosomal diseases of any type. Future parents all you need to do is donate blood. Those who already have a child with a genetic disease in the family must do this in without fail before re-pregnancy.

Mutational variability occurs in the event of the appearance of mutations - persistent changes in the genotype (i.e. DNA molecules), which can affect entire chromosomes, their parts or individual genes.

Mutations can be beneficial, harmful, or neutral. According to the modern classification, mutations are usually divided into the following groups.

1. Genomic mutations associated with a change in the number of chromosomes. Of particular interest is POLYPLOIDY - a multiple increase in the number of chromosomes, i.e. instead of a 2n chromosome set, a set of 3n,4n,5n or more appears. The occurrence of polyploidy is associated with a violation of the mechanism of cell division. In particular, nondisjunction of homologous chromosomes during the first division of meiosis leads to the appearance of gametes with a 2n set of chromosomes.

Polyploidy is widespread in plants and much less frequently in animals (roundworm, silkworm, some amphibians). Polyploid organisms tend to be more large size, enhanced synthesis of organic substances, which makes them especially valuable for breeding work.

A change in the number of chromosomes associated with the addition or loss of individual chromosomes is called aneuploidy. An aneuploidy mutation can be written as 2n-1, 2n+1, 2n-2, etc. Aneuploidy is characteristic of all animals and plants. In humans, a number of diseases are associated with aneuploidy. For example, Down's disease is associated with the presence of extra chromosome in the 21st pair.

2. Chromosomal mutations - this is a rearrangement of chromosomes, a change in their structure. Separate sections of chromosomes can be lost, doubled, change their position.

Schematically, this can be shown as follows:

ABCDE normal gene order

ABBCDE duplication of a segment of a chromosome

ABDE loss of one section

ABEDC 180 degree turn

ABCFG region exchange with non-homologous chromosome

Like genomic mutations, chromosomal mutations play a role huge role in evolutionary processes.

3. Gene mutations associated with a change in the composition or sequence of DNA nucleotides within a gene. Gene mutations are the most important of all mutation categories.

Protein synthesis is based on the correspondence between the arrangement of nucleotides in a gene and the order of amino acids in a protein molecule. The occurrence of gene mutations (changes in the composition and sequence of nucleotides) changes the composition of the corresponding enzyme proteins and, as a result, leads to phenotypic changes. Mutations can affect all features of the morphology, physiology and biochemistry of organisms. Many human hereditary diseases are also caused by gene mutations.

Mutations in natural conditions are rare - one mutation of a particular gene per 1000-100000 cells. But the mutation process goes on constantly, there is a constant accumulation of mutations in genotypes. And if we take into account that the number of genes in the body is large, then we can say that in the genotypes of all living organisms there is a significant number of gene mutations.

Mutations are the biggest biological factor, causing a huge hereditary variability of organisms, which provides material for evolution.

Mutations can be caused by natural disturbances in cell metabolism (spontaneous mutations), and the action various factors environment (induced mutations). Factors that cause mutations are called mutagens. Mutagens can be physical factors- radiation, temperature.... Biological mutagens include viruses capable of transferring genes between organisms of not only close, but distant systematic groups.

Human economic activity has brought a huge amount of mutagens into the biosphere.

Most mutations are unfavorable for the life of an individual, but sometimes mutations occur that may be of interest to breeding scientists. Currently, methods of site-directed mutagenesis have been developed.

1. According to the nature of the change in the phenotype, mutations can be biochemical, physiological, anatomical and morphological.

2. According to the degree of adaptability, mutations are divided into beneficial and harmful. Harmful - can be lethal and cause the death of the organism even in embryonic development.

More often, mutations are harmful, since traits are normally the result of selection and adapt the organism to its environment. Mutation always changes adaptation. The degree of its usefulness or uselessness is determined by time. If a mutation allows an organism to better adapt, it gives new chance survive, it is "picked up" by selection and fixed in the population.

3. Mutations are direct and reverse. The latter are much less common. Usually, a direct mutation is associated with a defect in the function of the gene. The probability of a secondary mutation in the opposite direction at the same point is very small, other genes mutate more often.

Mutations are more often recessive, since dominant ones appear immediately and are easily "rejected" by selection.

4. According to the nature of the change in the genotype, mutations are divided into gene, chromosomal and genomic.

Gene, or point, mutations - a change in a nucleotide in one gene in a DNA molecule, leading to the formation of an abnormal gene, and, consequently, an abnormal protein structure and the development of an abnormal trait. A gene mutation is the result of a "mistake" in DNA replication.

The result of a gene mutation in humans are diseases such as sickle cell anemia, phenylketonuria, color blindness, hemophilia. As a result of a gene mutation, new alleles of genes arise, which is important for the evolutionary process.

Chromosomal mutations - changes in the structure of chromosomes, chromosomal rearrangements. The main types of chromosomal mutations can be distinguished:

a) deletion - loss of a chromosome segment;

b) translocation - the transfer of part of the chromosomes to another non-homologous chromosome, as a result - a change in the linkage group of genes;

c) inversion - rotation of a chromosome segment by 180 °;

d) duplication - doubling of genes in certain area chromosomes.

Chromosomal mutations lead to a change in the functioning of genes and are important in the evolution of a species.

Genomic mutations - changes in the number of chromosomes in a cell, the appearance of an extra or loss of a chromosome as a result of a violation in meiosis. A multiple increase in the number of chromosomes is called polyploidy (3n, 4/r, etc.). This type of mutation is common in plants. Many cultivated plants are polyploid in relation to their wild ancestors. An increase in chromosomes by one or two in animals leads to anomalies in the development or death of the organism. Example: Down syndrome in humans - trisomy for the 21st pair, in total there are 47 chromosomes in a cell. Mutations can be obtained artificially with the help of radiation, X-rays, ultraviolet, chemical agents, and thermal exposure.

The law of homological series N.I. Vavilov. Russian biologist N.I. Vavilov established the nature of the occurrence of mutations in closely related species: “Genera and species that are genetically close are characterized by similar series of hereditary variability with such regularity that, knowing the number of forms within the same species, one can foresee the occurrence parallel forms in other species and genera.

The discovery of the law facilitated the search for hereditary deviations. Knowing the variability and mutations in one species, one can foresee the possibility of their appearance in related species, which is important in breeding.



This brochure contains information about what is chromosomal abnormalities how they can be inherited, and what problems can be associated with them. This booklet cannot replace your conversation with your doctor, but it can help you discuss your concerns.

In order to better understand what chromosomal disorders are, it will be helpful to first know what genes and chromosomes are.

What are genes and chromosomes?

Our body is made up of millions of cells. Most cells contain a complete set of genes. Humans have thousands of genes. Genes can be compared to instructions that are used to control growth and coordinate the work of the whole organism. Genes are responsible for many traits of our body, such as eye color, blood type, or height.

Genes are located on thread-like structures called chromosomes. Normally, most body cells contain 46 chromosomes. Chromosomes are passed on to us from our parents - 23 from mom and 23 from dad, so we often look like our parents. So we have two sets of 23 chromosomes, or 23 pairs of chromosomes. Since genes are located on chromosomes, we inherit two copies of each gene, one copy from each parent. Chromosomes (and therefore genes) are made up of chemical compound called DNA.

Figure 1: Genes, chromosomes and DNA

Chromosomes (see Figure 2), numbered 1 to 22, are the same in males and females. Such chromosomes are called autosomes. Chromosomes of the 23rd pair are different in women and men, and they are called sex chromosomes. There are 2 variants of sex chromosomes: X-chromosome and Y-chromosome. Normally, women have two X chromosomes (XX), one of them is transmitted from the mother, the other from the father. Normally, males have one X chromosome and one Y chromosome (XY), with the X chromosome inherited from the mother and the Y chromosome from the father. So, in Figure 2, the male chromosomes are shown, since the last, 23rd, pair is represented by the XY combination.

Figure 2: 23 pairs of chromosomes distributed by size; chromosome number 1 is the largest. The last two chromosomes are the sex chromosomes.

Chromosomal changes

The correct chromosome set is very important for normal human development. This is due to the fact that the genes that give “instructions for action” to the cells of our body are located on the chromosomes. Any change in the number, size or structure of our chromosomes could mean a change in the number or sequence genetic information. Such changes can lead to learning difficulties, developmental delays, and other health problems in the child.

Chromosomal changes can be inherited from parents. Most often, chromosomal changes occur at the stage of egg or sperm formation, or during fertilization (newly occurring mutations, or de novo mutations). These changes cannot be controlled.

There are two main types of chromosomal changes. Change in the number of chromosomes. With such a change, there is an increase or decrease in the number of copies of any chromosome. Change in the structure of chromosomes. With such a change, the material of any chromosome is damaged, or the sequence of genes is changed. Perhaps the appearance of additional or loss of part of the original chromosomal material.

In this brochure, we will look at chromosomal deletions, duplications, insertions, inversions and ring chromosomes. If you are interested in information about chromosomal translocations, please refer to the brochure "Chromosomal Translocations".

Change in the number of chromosomes.

Normally, each human cell contains 46 chromosomes. However, sometimes a baby is born with either more or fewer chromosomes. In this case, there is, respectively, either an excess or an insufficient number of genes necessary for regulating the growth and development of the organism.

One of the most common examples genetic disease caused by an excess number of chromosomes is Down syndrome. In the cells of people with this disease, there are 47 chromosomes instead of the usual 46, since there are three copies of the 21st chromosome instead of two. Other examples of diseases caused by an excess number of chromosomes are Edwards and Patau syndromes.

Figure 3: Chromosomes of a girl (the last pair of XX chromosomes) with Down syndrome. Three copies of chromosome 21 are visible instead of two.

Change in the structure of chromosomes.

Changes in the structure of chromosomes occur when the material of a particular chromosome is damaged or the sequence of genes is changed. Structural changes also include an excess or loss of part of the chromosomal material. This can happen in several ways, described below.

Changes in the structure of chromosomes can be very small, and it can be difficult for specialists in laboratories to detect them. However, even if structural change found, it is often difficult to predict the impact of this change on the health of a particular child. This can be frustrating for parents who want comprehensive information about their child's future.

Translocations

If you would like to learn more about translocations, please refer to the Brochure Chromosomal Translocations.

Deletions

The term "chromosomal deletion" means that part of the chromosome is missing or shortened. A deletion can happen on any chromosome and throughout any part of the chromosome. The deletion can be of any size. If the material (genes) lost during the deletion contained important information for the body, the child may experience learning difficulties, developmental delay and other health problems. The severity of these manifestations depends on the size of the lost part and localization within the chromosome. An example of such a disease is Joubert's syndrome.

Duplications

The term "chromosomal duplication" means that part of the chromosome is doubled, and because of this, an excess of genetic information occurs. This excess chromosome material means the body is getting too big number"instructions" and this can lead to learning difficulties, developmental delays and other health problems in the child. An example of a disease caused by a duplication of a portion of chromosomal material is type IA motor sensory neuropathy.

Insertions

Chromosomal insertion (insert) means that part of the material of the chromosome was "out of place" on the same or on another chromosome. If the total amount of chromosomal material has not changed, then such a person is usually healthy. However, if such a movement leads to a change in the amount of chromosomal material, then the person may experience learning difficulties, developmental delay and other health problems for the child.

Ring chromosomes

The term “ring chromosome” means that the ends of the chromosome have joined, and the chromosome has acquired the shape of a ring (normally, human chromosomes have a linear structure). This usually happens when both ends of the same chromosome are shortened. The remaining ends of the chromosome become "sticky" and join together to form a "ring". The consequences of the formation of ring chromosomes for an organism depend on the size of the deletions at the ends of the chromosome.

Inversions

Chromosomal inversion means a change in the chromosome in which part of the chromosome is unfolded, and the genes in this region are located in reverse order. In most cases, the carrier of the inversion is healthy.

If a parent has an unusual chromosomal rearrangement, how might this affect the child?

There are several possible outcomes of each pregnancy:

• A child can get a completely normal set of chromosomes.
• A child can inherit the same chromosomal rearrangement that the parent has.
• The child may have learning difficulties, developmental delays, or other health problems.
• Spontaneous abortion is possible.

Thus, healthy children can be born to a carrier of a chromosomal rearrangement, and in many cases this is exactly what happens. Since each rebuild is unique, your specific situation should be discussed with a geneticist. It often happens that a child is born with a chromosomal rearrangement, despite the fact that the chromosome set of the parents is normal. Such rearrangements are called newly emerged, or emerging “de novo” (from Latin word). In these cases, the risk of re-birth of a child with a chromosomal rearrangement in the same parents is very small.

Diagnosis of chromosomal rearrangements

It is possible to conduct a genetic analysis to identify the carriage of a chromosomal rearrangement. A blood sample is taken for analysis, and the blood cells are examined in a specialized laboratory to detect chromosomal rearrangements. This analysis is called karyotyping. It is also possible to perform a test during pregnancy to evaluate the chromosomes of the fetus. Such an analysis is called prenatal diagnosis, and this issue should be discussed with a geneticist. More detailed information on this topic is presented in the brochures "Biopsy of the chorionic villi" and "Amniocentesis".

How it affects other family members

If a chromosomal rearrangement is found in one of the family members, you may want to discuss this issue with other family members. This will enable other relatives, if desired, to undergo an examination (analysis of chromosomes in blood cells) to determine the carriage of a chromosomal rearrangement. This may be especially important for relatives who already have children or are planning a pregnancy. If they are not carriers of a chromosomal rearrangement, they cannot pass it on to their children. If they are carriers, they may be asked to be screened during pregnancy to analyze the fetal chromosomes.

Some people find it difficult to discuss chromosomal rearrangement problems with family members. They may be afraid of disturbing family members. In some families, people experience difficulties in communication because of this and lose mutual understanding with relatives. Geneticists usually have great experience in dealing with similar family situations and can help you discuss the problem with other family members.

What is important to remember

• Chromosomal rearrangement can either be inherited from parents or occur during fertilization.
• Perestroika cannot be corrected - it remains for life.
• Restructuring is not contagious, for example, its carrier can be a blood donor.
• People often feel guilty about the fact that their family has such a problem as chromosomal rearrangement. It is important to remember that this is not anyone's fault or a consequence of anyone's actions.
• Most carriers of balanced rearrangements can have healthy children.

Waiting for the birth of a child is the most beautiful time for parents, but also the worst. Many are worried that the baby may be born with some kind of handicap, physical or mental disabilities.

Science does not stand still, it is possible to check the baby for developmental abnormalities at a short time in pregnancy. Almost all of these tests can show whether everything is fine with the child.

Why does it happen that completely different children can be born to the same parents - healthy child and a child with disabilities? It is determined by genes. In the birth of an underdeveloped baby or a child with physical disabilities, gene mutations associated with changes in the structure of DNA. Let's talk about this in more detail. Consider how this happens, what gene mutations are, and their causes.

What are mutations?

Mutations are physiological and biological changes in cells in the structure of DNA. The reason may be radiation (during pregnancy, you can not take x-rays, for the presence of injuries and fractures), ultra-violet rays(long exposure to the sun during pregnancy or being in a room with lamps on ultraviolet light). Also, such mutations can be inherited from ancestors. All of them are divided into types.

Gene mutations with a change in the structure of chromosomes or their number

These are mutations in which the structure and number of chromosomes are changed. Chromosomal regions can fall out or double, move to a non-homologous zone, turn one hundred and eighty degrees from the norm.

The reasons for the appearance of such a mutation is a violation in crossover.

Gene mutations are associated with a change in the structure of chromosomes or their number, they are the cause of serious disorders and illnesses in a baby. Such diseases are incurable.

Types of chromosomal mutations

In total, two types of basic chromosomal mutations are distinguished: numerical and structural. Aneuploidies are types according to the number of chromosomes, that is, when gene mutations are associated with a change in the number of chromosomes. This is the emergence of an additional or several of the latter, the loss of any of them.

Gene mutations are associated with a change in structure in the case when chromosomes break and then reunite, violating the normal configuration.

Types of numerical chromosomes

According to the number of chromosomes, mutations are divided into aneuploidy, that is, species. Consider the main ones, find out the difference.

• trisomy

Trisomy is the occurrence of an extra chromosome in the karyotype. The most common occurrence is the appearance of the twenty-first chromosome. It becomes the cause of Down syndrome, or, as this disease is also called, trisomy of the twenty-first chromosome.

Patau's syndrome is detected on the thirteenth, and on the eighteenth chromosome they are diagnosed. These are all autosomal trisomies. Other trisomies are not viable, they die in the womb and are lost in spontaneous abortions. Those individuals who have additional sex chromosomes (X, Y) are viable. Clinical manifestation these mutations are very few.

Gene mutations associated with a change in number occur for certain reasons. Trisomy most often occurs during divergence in anaphase (meiosis 1). The result of this discrepancy is that both chromosomes fall into only one of the two daughter cells, the second one is empty.

Less commonly, nondisjunction of chromosomes may occur. This phenomenon is called a violation in the divergence of sister chromatids. Occurs in meiosis 2. This is exactly the case when two completely identical chromosomes lodge in one gamete, causing a trisomic zygote. Nondisjunction occurs in the early stages of the cleavage process of an egg that has been fertilized. Thus, a clone of mutant cells arises, which can cover a large or a smaller part fabrics. Sometimes it manifests itself clinically.

Many associate the twenty-first chromosome with the age of a pregnant woman, but this factor is up to today does not have unequivocal confirmation. The reasons why chromosomes do not separate remain unknown.

• monosomy

Monosomy is the absence of any of the autosomes. If this happens, then in most cases the fetus cannot be borne, premature birth occurs on early dates. The exception is monosomy due to the twenty-first chromosome. The reason why monosomy occurs can be both the nondisjunction of chromosomes and the loss of a chromosome during its journey in anaphase to the cell.

For sex chromosomes, monosomy leads to the formation of a fetus with an XO karyotype. The clinical manifestation of such a karyotype is Turner's syndrome. In eighty percent of cases out of a hundred, the appearance of monosomy on the X chromosome is due to a violation of meiosis of the father of the child. This is due to the nondisjunction of the X and Y chromosomes. Basically, a fetus with an XO karyotype dies in the womb.

According to the sex chromosomes, trisomy is divided into three types: 47 XXY, 47 XXX, 47 XYY. is trisomy 47XXY. With such a karyotype, the chances of carrying a child are divided fifty to fifty. The cause of this syndrome may be the nondisjunction of the X chromosomes or the nondisjunction of X and Y of spermatogenesis. The second and third karyotypes can occur in only one out of a thousand pregnant women, they practically do not manifest themselves and in most cases are discovered by specialists quite by accident.

• polyploidy

These are gene mutations associated with a change in the haploid set of chromosomes. These sets can be tripled or quadrupled. Triploidy is most often diagnosed only when a spontaneous abortion has occurred. There were several cases when the mother managed to bear such a baby, but they all died before reaching even a month of age. The mechanisms of gene mutations in the case of triplodia are determined by the complete divergence and non-divergence of all chromosome sets of either female or male germ cells. Also, a double fertilization of one egg can serve as a mechanism. In this case, the placenta degenerates. Such a rebirth is called a cystic skid. As a rule, such changes lead to the development of mental and physiological disorders in the baby, termination of pregnancy.

What gene mutations are associated with a change in the structure of chromosomes

Structural changes in chromosomes are the result of rupture (destruction) of the chromosome. As a result, these chromosomes are connected, violating their former appearance. These modifications can be unbalanced and balanced. Balanced have no excess or lack of material, so they do not appear. They can appear only if there was a gene that is functionally important at the site of the destruction of the chromosome. A balanced set may have unbalanced gametes. As a result, the fertilization of the egg with such a gamete can cause the appearance of a fetus with an unbalanced chromosome set. With such a set, the fetus develops whole line malformations, severe types of pathology appear.

Types of structural modifications

Gene mutations occur at the level of gamete formation. It is impossible to prevent this process, just as it is impossible to know for sure that it can happen. There are several types of structural modifications.

• deletions

This change is associated with the loss of part of the chromosome. After such a break, the chromosome becomes shorter, and its torn off part is lost during further cell division. Interstitial deletions are the case when one chromosome breaks in several places at once. Such chromosomes usually create a non-viable fetus. But there are also cases when babies survived, but because of such a set of chromosomes, they had Wolf-Hirshhorn syndrome, “cat's cry”.

• duplications

These gene mutations occur at the level of organization of doubled DNA sections. Basically, duplication cannot cause such pathologies that cause deletions.

• translocations

Translocation occurs due to the transfer of genetic material from one chromosome to another. If a break occurs simultaneously in several chromosomes and they exchange segments, then this causes a reciprocal translocation. The karyotype of such a translocation has only forty-six chromosomes. The translocation itself is revealed only when detailed analysis and study of the chromosome.

Changing the nucleotide sequence

Gene mutations are associated with a change in the sequence of nucleotides, when they are expressed in a modification of the structures of certain sections of DNA. According to the consequences, such mutations are divided into two types - without a frameshift and with a shift. To know exactly the causes of changes in DNA sections, you need to consider each type separately.

Mutation without frameshift

These gene mutations are associated with the change and replacement of nucleotide pairs in the DNA structure. With such substitutions, DNA length is not lost, but amino acids can be lost and replaced. There is a possibility that the structure of the protein will be preserved, this will serve. Let us consider in detail both variants of development: with and without replacement of amino acids.

Amino acid substitution mutation

Changes in amino acid residues in polypeptides are called missense mutations. There are four chains in the human hemoglobin molecule - two "a" (it is located on the sixteenth chromosome) and two "b" (coding on the eleventh chromosome). If "b" - the chain is normal, and it contains one hundred and forty-six amino acid residues, and the sixth is glutamine, then hemoglobin will be normal. In this case, glutamic acid must be encoded by the GAA triplet. If, due to a mutation, GAA is replaced by GTA, then instead of glutamic acid, valine is formed in the hemoglobin molecule. Thus, instead of normal hemoglobin HbA, another hemoglobin HbS will appear. Thus, the replacement of one amino acid and one nucleotide will cause a serious serious illness - sickle cell anemia.

This disease is manifested by the fact that red blood cells become shaped like a sickle. In this form, they are not able to deliver oxygen normally. If on cellular level homozygotes have the formula HbS/HbS, this leads to the death of the child in the very early childhood. If the formula is HbA / HbS, then the erythrocytes have a weak form of change. Such slight change It has useful quality- body resistance to malaria. In those countries where there is a danger of contracting malaria the same as in Siberia with a cold, this change has a beneficial quality.

Mutation without amino acid substitution

Nucleotide substitutions without amino acid exchange are called Seimsense mutations. If GAA is replaced by GAG in the DNA region encoding the "b" chain, then due to the fact that it will be in excess, the replacement of glutamic acid cannot occur. The structure of the chain will not be changed, there will be no modifications in the erythrocytes.

Frameshift Mutations

Such gene mutations are associated with a change in the length of DNA. The length can become shorter or longer, depending on the loss or gain of nucleotide pairs. Thus, the entire structure of the protein will be completely changed.

Intragenous suppression may occur. This phenomenon occurs when there is room for two mutations to cancel each other out. This is the moment when a nucleotide pair is added after one has been lost, and vice versa.

Nonsense Mutations

it special group mutations. It occurs rarely, in its case, the appearance of stop codons. This can happen both with the loss of nucleotide pairs and with their addition. When stop codons appear, polypeptide synthesis stops completely. This can create null alleles. None of the proteins will match this.

There is such a thing as intergenic suppression. This is such a phenomenon when the mutation of some genes suppresses mutations in others.

Are there any changes during pregnancy?

Gene mutations associated with a change in the number of chromosomes can in most cases be identified. To find out if the fetus has malformations and pathologies, screening is prescribed in the first weeks of pregnancy (from ten to thirteen weeks). This is a series of simple examinations: blood sampling from a finger and a vein, ultrasound. On the ultrasound examination the fetus is examined in accordance with the parameters of all limbs, nose and head. These parameters, with a strong non-compliance with the norms, indicate that the baby has developmental defects. This diagnosis is confirmed or refuted based on the results of a blood test.

Also under the close supervision of physicians are expectant mothers, whose babies may develop mutations at the gene level, which are inherited. That is, these are women in whose relatives there were cases of the birth of a child with mental or physical disabilities, identified Down syndrome, Patau and other genetic diseases.