Biological mutations. Gene mutations

Mutation means change in the amount and structure of DNA in a cell or organism. In other words, mutation is a change in genotype. A feature of a change in genotype is that this change as a result of mitosis or meiosis can be transmitted to subsequent generations of cells.

Most often, mutations mean a small change in the sequence of DNA nucleotides (changes in one gene). These are the so-called. However, in addition to them, there are also when changes affect large sections of DNA, or the number of chromosomes changes.

As a result of mutation, the body may suddenly develop a new trait.

The idea that mutation is the cause of the appearance of new traits transmitted through generations was first expressed by Hugo de Vries in 1901. Later, mutations in Drosophila were studied by T. Morgan and his school.

Mutation - harm or benefit?

Mutations that occur in “insignificant” (“silent”) sections of DNA do not change the characteristics of the organism and can be easily passed on from generation to generation (natural selection will not act on them). Such mutations can be considered neutral. Mutations are also neutral when a section of a gene is replaced by a synonymous one. In this case, although the sequence of nucleotides in a certain region will be different, the same protein (with the same amino acid sequence) will be synthesized.

However, a mutation can affect a significant gene, change the amino acid sequence of the synthesized protein, and, consequently, cause a change in the characteristics of the organism. Subsequently, if the concentration of mutation in the population reaches a certain level, this will lead to a change characteristic feature the entire population.

In living nature, mutations arise as errors in DNA, so they are all a priori harmful. Most mutations reduce the viability of the organism and cause various diseases. Mutations that occur in somatic cells are not transmitted to the next generation, but as a result of mitosis, daughter cells are formed that make up a particular tissue. Often somatic mutations lead to the formation of various tumors and other diseases.

Mutations that occur in germ cells can be passed on to the next generation. Under stable environmental conditions, almost all changes in the genotype are harmful. But if environmental conditions change, it may turn out that a previously harmful mutation will become beneficial.

For example, a mutation that causes short wings in an insect is likely to be harmful in a population living in areas where there is no strong wind. This mutation will be akin to a deformity or a disease. Insects possessing it will have difficulty finding mating partners. But if stronger winds begin to blow in the area (for example, as a result of a fire, a section of the forest was destroyed), then insects with long wings will be blown away by the wind, and it will be more difficult for them to move. In such conditions, short-winged individuals may gain an advantage. They will find partners and food more often than longwings. After some time, there will be more short-winged mutants in the population. Thus, the mutation will take hold and become normal.

Mutations are the basis of natural selection and this is their main benefit. For the body, the overwhelming number of mutations is harmful.

Why do mutations occur?

In nature, mutations occur randomly and spontaneously. That is, any gene can mutate at any time. However, the frequency of mutations varies among different organisms and cells. For example, it is related to the duration life cycle: the shorter it is, the more often mutations occur. Thus, mutations occur much more often in bacteria than in eukaryotic organisms.

Except spontaneous mutations(occurring in natural conditions) there are induced(by a person in laboratory conditions or unfavorable environmental conditions) mutations.

Basically, mutations arise as a result of errors during replication (doubling), DNA repair (restoration), unequal crossing over, incorrect chromosome segregation in meiosis, etc.

This is how damaged DNA sections are constantly restored (repaired) in cells. However, if, for various reasons, the repair mechanisms are disrupted, then errors in the DNA will remain and accumulate.

The result of a replication error is the replacement of one nucleotide in a DNA chain with another.

What causes mutations?

Increased levels of mutations are caused by X-rays, ultraviolet and gamma rays. Mutagens also include α- and β-particles, neutrons, cosmic radiation (all these are high-energy particles).

Mutagen- this is something that can cause mutation.

In addition to various radiations, many have a mutagenic effect. chemicals: formaldehyde, colchicine, tobacco components, pesticides, preservatives, some medicines etc.

Mutations are changes in the DNA of a cell. Occur under the influence of ultraviolet radiation, radiation (X-rays), etc. They are inherited and serve as material for natural selection. differences from modifications

Gene mutations are changes in the structure of one gene. This is a change in the nucleotide sequence: deletion, insertion, substitution, etc. For example, replacing A with T. Causes: violations during DNA doubling (replication). Examples: sickle cell anemia, phenylketonuria.

Chromosomal mutations are changes in the structure of chromosomes: loss of a section, doubling of a section, rotation of a section by 180 degrees, transfer of a section to another (non-homologous) chromosome, etc. The reasons are violations during crossing over. Example: Cry Cat Syndrome.

Genomic mutations are changes in the number of chromosomes. The causes are disturbances in the divergence of chromosomes.

Polyploidy – multiple changes (several times, for example, 12 → 24). It does not occur in animals; in plants it leads to an increase in size.

Aneuploidy is a change in one or two chromosomes. For example, one extra twenty-first chromosome leads to Down syndrome (with a total number of chromosomes of 47).

Cytoplasmic mutations are changes in the DNA of mitochondria and plastids. They are transmitted only through the female line, because mitochondria and plastids from sperm do not enter the zygote. An example in plants is variegation.

Somatic - mutations in somatic cells (cells of the body; there can be four of the above types). During sexual reproduction they are not inherited. Transmitted during vegetative propagation in plants, budding and fragmentation in coelenterates (hydra).

If we consider the relationship between cell reproduction and their maturation, then all genes of somatic cells can be divided into three large groups:

Genes that control reproduction, or autosynthetic genes (AS genes);

Genes that regulate specific cell activity (movement, excretion, irritability, digestion foreign bodies), or heterosynthetic genes (HS genes);

Genes that carry information for self-preservation (CC genes), for example, genes that regulate cell respiration.

These names indicate that the metabolism of AS-type cells is aimed only at the reproduction of their own kind, and the specialized activity of GS cells is aimed at maintaining the entire organism. In young cells, the activity of AC and CC genes is primarily manifested, and GS genes are in a “dormant” state. Maturation is always determined by some inducer (factor). During differentiation, GS genes are gradually activated and the synthesis of specialized proteins begins. In cells of average maturity, AC genes are still active and the activity of GS genes is already manifested. In other words, for the simultaneous reproduction and growth of cells, the activity of specific substances is required. At the same time, a new regulatory gene (regulator) is activated, which determines the synthesis of an intracellular inhibitor. This inhibitor binds to AS genes, blocking them. Gradually, reproduction regulated by AS genes stops, and mature dead-end cells are no longer capable of dividing.

Somatic mutations are changes of a hereditary nature in somatic cells that occur at different stages of development of an individual. They are often not inherited, but remain as long as the organism affected by the mutation lives. In this case, they will be inherited only in a specific cell clone that originated from the mutant cell. It is known that mutations in somatic cell genes can in some cases cause cancer. Mutations that occur in somatic tissues are called somatic mutations. Somatic cells constitute a population formed by asexual reproduction (division) of cells. Somatic mutations cause genotypic diversity in tissues, are often not inherited and are limited to the individual in which they arose. Somatic mutations occur in diploid cells, therefore they appear only with dominant genes or with recessive ones, but in a homozygous state. The earlier in human embryogenesis a mutation occurs, the larger the area of ​​somatic cells deviates from the norm. Malignant growth is caused by carcinogens, among which the most negative are penetrating radiation and active chemical compounds (substances), and although somatic mutations are not inherited, they reduce the reproductive capabilities of the organism in which they arose.

Carcinogenesis is a mechanism for the implementation of external and internal factors that cause the transformation of a normal cell into a cancerous one and contribute to the growth and spread of a malignant neoplasm. Carcinogenesis contains two different groups of processes: damage and repair of these damage (pathogenic and sanogenic). These processes can be placed schematically at three levels - cell, organ, organism, understanding that from the very beginning all processes are interconnected and not sequential. The process of development of a malignant tumor, initiated by different factors, is basically similar and therefore, with some generalization, we can talk about the monopathogenetic nature of cancer.

The mechanism of carcinogenesis on a cellular basis is multi-stage, that is, the main phases of carcinogenesis (initiation, promotion) also have “subphases” that depend on the qualitative characteristics of the carcinogens themselves and on the characteristics of individual cells, in particular the phases of their cell cycle. The mechanisms of chemical and physical carcinogenesis as the main initiators of cancer can be described in a simplified, schematized form, highlighting only the main components. It is believed that there are no threshold (permissible) concentrations of both chemical and radiation carcinogens and it is impossible to determine them. The reason for this is the presence of a huge number of carcinogens in the environment and the need to take into account their synergistic effect.

All carcinogenic substances, based on their origin, can be divided into two large groups - exogenous and endogenous. Exogenous carcinogens. Exogenous substances include carcinogenic substances found in the external environment. The appearance of tumors in people of certain professions was noted back in the 18th century. It has now been established that a wide variety of chemicals from different classes of compounds - hydrocarbons, aminoazo compounds, amines, fluorenes, etc. - can cause tumors. The doctrine of endogenous carcinogens received experimental evidence in the works of L. M. Shabad et al. on the detection of carcinogenic activity in benzene extracts from the liver of people who died from cancer. This doctrine was enriched with specific content in connection with the discovery of carcinogenic activity in aromatic derivatives of tryptophan, methoxyindoles, tyrosine metabolites and, accordingly, the discovery of a perverted metabolism of aromatic amino acids in patients with different types of tumors.

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✪ Types of mutations. Gene mutations

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✪ Types of mutations. Genomic and chromosomal mutations

✪ Biology lesson No. 53. Mutations. Types of mutations.

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Nick Vujicic was born with a rare hereditary disease called Tetra-Amelia syndrome. The boy was missing full arms and legs, but had one partial foot with two fused toes; this allowed the boy, after surgical separation of his fingers, to learn to walk, swim, skateboard, work on a computer and write. After experiencing disability as a child, he learned to live with his disability, sharing his experiences with others and becoming a world-renowned motivational speaker. In 2012, Nick Vujicic got married. And subsequently the couple had 2 absolutely healthy sons. In 2015, a baby was born in Egypt with one eye in the middle of his forehead. Doctors said the newborn boy suffered from cyclopia, an unusual condition whose name comes from the one-eyed giants of Greek mythology. The disease was a consequence of radiation exposure in the womb. Cyclopia is one of the rarest forms of birth defects. Babies born with this condition often die soon after birth because they often have other serious defects, including damage to the heart and other organs. In the USA, in the state of Iowa, Isaac Brown lives, who has been diagnosed with a very unusual disease. The essence of this disease is that the child does not feel pain. Because of this, Isaac's parents are forced to constantly monitor their son to prevent serious injury to the child. The boy's ability not to feel pain is the result of a rare genetic disease. Of course, when a boy is injured, he experiences pain, only these sensations are several times weaker than in other people. After breaking his leg, Isaac realized that there was simply something wrong with his leg, since he could not walk as usual, but there was no pain. In addition to the fact that the baby does not feel pain, during the examination he was found to have anhidrosis, that is, there is no ability to regulate his own body temperature. Experts are currently studying DNA samples from the boy, hoping to find a defect in the genes and develop methods for treating such a disease. A little American girl named Gabby Williams has a rare condition. She will remain forever young. Now she is 11 years old and weighs 5 kilograms. At the same time, she has the face and body of a child. Her strange deviation was dubbed real story Benjamin Button, because the girl ages a year in four years. And this is an amazing phenomenon, over which dozens of specialists are racking their brains. When she was born, she was purple and blind. Tests showed she had a brain abnormality and her optic nerve was damaged. She has two heart defects, a cleft palate, and an abnormal swallowing reflex, so she can only eat through a tube in her nose. The girl is also completely mute. The baby can only cry or sometimes smile. There are no deviations in DNA, but Gabby hardly ages in comparison with other people, and no one knows what the reason is. Javier Botet suffers from a rare genetic disorder known as Marfan Syndrome. People with this disease are tall, thin, and have elongated limbs and fingers. Their bones are not only elongated, but also have amazing flexibility. It is worth noting that without treatment and care, those suffering from Marfan Syndrome rarely live past the age of forty. Javier Botet is 2 meters tall and weighs only 45 kg. These specific external data, features of the physical structure and genetic system helped Botet become “one of the people” in horror films. He played the terrifyingly thin zombie in the Report trilogy, as well as creepy ghosts in Mom, Crimson Peak and The Conjuring 2.

Causes of mutations

Mutations are divided into spontaneous And induced. Spontaneous mutations occur spontaneously throughout the life of an organism under normal environmental conditions with a frequency of about 10 − 9 (\displaystyle 10^(-9)) - 10 − 12 (\displaystyle 10^(-12)) per nucleotide for the cellular generation of an organism.

Induced mutations are heritable changes in the genome that arise as a result of certain mutagenic effects in artificial (experimental) conditions or under adverse environmental influences.

Mutations appear constantly during processes occurring in a living cell. The main processes leading to the occurrence of mutations are DNA replication, DNA repair disorders, transcription and genetic recombination.

Relationship between mutations and DNA replication

Many spontaneous chemical changes in nucleotides result in mutations that occur during replication. For example, due to the deamination of cytosine opposite guanine, uracil can be included in the DNA chain (a U-G pair is formed instead of the canonical pairs C-G). During DNA replication, opposite uracil, adenine is included in the new chain, forming couple U-A, and during the next replication it is replaced by a T-A pair, that is, a transition occurs (a point replacement of a pyrimidine with another pyrimidine or a purine with another purine).

Relationship between mutations and DNA recombination

Of the processes associated with recombination, unequal crossing over most often leads to mutations. It usually occurs in cases where there are several duplicated copies of the original gene on the chromosome that have retained a similar nucleotide sequence. As a result of unequal crossing over, duplication occurs in one of the recombinant chromosomes, and deletion occurs in the other.

Relationship between mutations and DNA repair

Tautomeric model of mutagenesis

It is assumed that one of the reasons for the formation of base substitution mutations is deamination of 5-methylcytosine, which can cause transitions from cytosine to thymine. Due to the deamination of the cytosine opposite it, uracil can be included in the DNA chain (a U-G pair is formed instead of the canonical C-G pair). During DNA replication opposite uracil, adenine is included in the new chain, a U-A pair is formed, and during the next replication it is replaced by a T-A pair, that is, a transition occurs (a point replacement of a pyrimidine with another pyrimidine or a purine with another purine).

Mutation classifications

There are several classifications of mutations based on various criteria. Möller proposed dividing mutations according to the nature of the change in the functioning of the gene into hypomorphic(altered alleles act in the same direction as wild-type alleles; only less is synthesized protein product), amorphous(a mutation looks like a complete loss of gene function, e.g. white in Drosophila), antimorphic(the mutant trait changes, for example, the color of the corn grain changes from purple to brown) and neomorphic.

Modern educational literature also uses a more formal classification based on the nature of changes in the structure of individual genes, chromosomes and the genome as a whole. Within this classification, the following types of mutations are distinguished:

• genomic;
• chromosomal;
• genetic.

A point mutation, or single base substitution, is a type of mutation in DNA or RNA that is characterized by the replacement of one nitrogenous base with another. The term also applies to pairwise nucleotide substitutions. The term point mutation also includes insertions and deletions of one or more nucleotides. There are several types of point mutations.

Complex mutations also occur. These are changes in DNA when one section of it is replaced by a section of a different length and a different nucleotide composition.

Point mutations can appear opposite damage to the DNA molecule that can stop DNA synthesis. For example, opposite cyclobutane pyrimidine dimers. Such mutations are called target mutations (from the word “target”). Cyclobutane pyrimidine dimers cause both targeted base substitution mutations and targeted frameshift mutations.

Sometimes point mutations occur in so-called undamaged regions of DNA, often in a small vicinity of photodimers. Such mutations are called untargeted base substitution mutations or untargeted frameshift mutations.

Point mutations do not always form immediately after exposure to a mutagen. Sometimes they appear after dozens of replication cycles. This phenomenon is called delayed mutations. If the genome is unstable, main reason education malignant tumors, the number of untargeted and delayed mutations increases sharply.

There are four possible genetic consequences of point mutations: 1) preservation of the meaning of the codon due to the degeneracy of the genetic code (synonymous nucleotide substitution), 2) change in the meaning of the codon, leading to the replacement of an amino acid in the corresponding place of the polypeptide chain (missense mutation), 3) formation of a meaningless codon with premature termination (nonsense mutation). There are three meaningless codons in the genetic code: amber - UAG, ocher - UAA and opal - UGA (in accordance with this, mutations leading to the formation of meaningless triplets are also named - for example, amber mutation), 4) reverse substitution (stop codon to sense codon).

By influence on gene expression mutations are divided into two categories: mutations such as base pair substitutions And reading frame shift type. The latter are deletions or insertions of nucleotides, the number of which is not a multiple of three, which is associated with the triplet nature of the genetic code.

The primary mutation is sometimes called direct mutation, and a mutation that restores the original structure of the gene is reverse mutation, or reversion. A return to the original phenotype in a mutant organism due to restoration of the function of the mutant gene often occurs not due to true reversion, but due to a mutation in another part of the same gene or even another non-allelic gene. In this case, the recurrent mutation is called a suppressor mutation. The genetic mechanisms due to which the mutant phenotype is suppressed are very diverse.

Kidney mutations(sports) - persistent somatic mutations occurring in the cells of plant growth points. Lead to clonal variability. They are preserved during vegetative propagation. Many varieties of cultivated plants are bud mutations.

Consequences of mutations for cells and organisms

Mutations that impair cell activity in a multicellular organism often lead to cell destruction (in particular, programmed cell death - apoptosis). If intra- and extracellular protective mechanisms do not recognize the mutation and the cell undergoes division, then the mutant gene will be passed on to all descendants of the cell and, most often, leads to the fact that all these cells begin to function differently.

In addition, the frequency of mutations of different genes and different regions within one gene naturally varies. It is also known that higher organisms use “targeted” (that is, occurring in certain sections of DNA) mutations in their mechanisms

How do harmful genes arise?

Although the main property of genes is accurate self-copying, due to which the hereditary transmission of many traits from parents to children occurs, this property is not absolute. The nature of the genetic material is dual. Genes also have the ability to change and acquire new properties. Such gene changes are called mutations. And it is gene mutations that create the variability necessary for the evolution of living matter and the diversity of life forms. Mutations occur in any cells of the body, but only genes from germ cells can be transmitted to offspring.

The reasons for mutations are that many environmental factors with which each organism interacts throughout life can disrupt the strict orderliness of the process of self-reproduction of genes and chromosomes as a whole, leading to errors in inheritance. Experiments have established the following factors that cause mutations: ionizing radiation, chemicals and high temperature. Obviously, all these factors exist in the natural human environment (for example, natural background radiation, cosmic radiation). Mutations have always existed as a completely common natural phenomenon.

Being essentially errors in the transmission of genetic material, mutations are random and undirected in nature, that is, they can be both beneficial and harmful and relatively neutral for the body.

Beneficial mutations are fixed in the course of evolution and form the basis for the progressive development of life on Earth, while harmful ones, which reduce viability, are, as it were, the other side of the coin. They underlie hereditary diseases in all their diversity.

There are two types of mutations:

• genetic (at the molecular level)
• and chromosomal (changing the number or structure of chromosomes at the cellular level)

Both of them can be caused by the same factors.

How often do mutations occur?
Is the appearance of a sick child often associated with a new mutation?

If mutations occurred too often, then variability in living nature would prevail over heredity and no stable forms of life would exist. Logic obviously dictates that mutations are rare events, at least much rarer than the possibility of preserving the properties of genes when transmitted from parents to children.

The actual frequency of mutations for individual human genes averages from 1:105 to 1:108. This means that approximately one in a million germ cells carries a new mutation in each generation. Or, in other words, although this is a simplification, we can say that for every million cases of normal gene transmission, there is one case of mutation. The important fact is that, once it has arisen, this or that new mutation can then be transmitted to subsequent generations, that is, fixed by the mechanism of inheritance, since reverse mutations that return the gene to its original state are just as rare.

In populations, the ratio of the number of mutants and those who inherited a harmful gene from their parents (segregants) among all patients depends both on the type of inheritance and on their ability to leave offspring. In classic recessive diseases, a harmful mutation can be transmitted unnoticed through many generations of healthy carriers until two carriers of the same harmful gene marry, and then almost every such case of the birth of a sick child is associated with inheritance, and not with a new mutation .

In dominant diseases, the proportion of mutants is inversely related to the fertility of patients. It is obvious that when a disease leads to early death or the inability of patients to have children, inheriting the disease from parents is impossible. If the disease does not affect life expectancy or the ability to have children, then, on the contrary, inherited cases will predominate, and new mutations will be rare in comparison.

For example, in one of the forms of dwarfism (dominant achondroplasia), for social and biological reasons, the reproduction of dwarfs is significantly lower than average; in this population group there are approximately 5 times fewer children compared to others. If we take the average reproduction factor as normal as 1, then for dwarfs it will be equal to 0.2. This means that 80% of sufferers in each generation are the result of a new mutation, and only 20% of sufferers inherit dwarfism from their parents.

In hereditary diseases that are genetically linked to sex, the proportion of mutants among sick boys and men also depends on the relative fertility of the patients, but here cases of inheritance from mothers will always predominate, even in those diseases where patients do not leave offspring at all. The maximum proportion of new mutations in such lethal diseases does not exceed 1/3 of the cases, since men account for exactly one third of the X chromosomes of the entire population, and two thirds of them occur in women, who, as a rule, are healthy.

Can I have a child with the mutation if I received an increased dose of radiation?

The negative consequences of environmental pollution, both chemical and radioactive, are the problem of the century. Geneticists encounter it not as rarely as we would like in a wide range of issues: from occupational hazards to the deterioration of the environmental situation as a result of accidents at nuclear power plants. And the concern, for example, of people who survived the Chernobyl tragedy is understandable.

The genetic consequences of environmental pollution are indeed associated with an increase in the frequency of mutations, including harmful ones, leading to hereditary diseases. However, these consequences, fortunately, are not so catastrophic as to speak of the danger of genetic degeneration of humanity, at least at the present stage. In addition, if we consider the problem in relation to specific individuals and families, then we can say with confidence that the risk of having a sick child due to radiation or other harmful effects as a result of mutation is never high.

Although the frequency of mutations is increasing, it is not so much as to exceed a tenth or even a hundredth of a percent. In any case, for any person, even those who have been clearly exposed to mutagenic factors, the risk of negative consequences for the offspring is much less than the genetic risk inherent in all people associated with the carriage of pathological genes inherited from their ancestors.

In addition, not all mutations lead to immediate manifestation in the form of a disease. In many cases, even if a child receives a new mutation from one of the parents, he will be born completely healthy. After all, a significant part of mutations are recessive, that is, they do not manifest their harmful effects from carriers. And there are practically no cases where, with initially normal genes of both parents, a child receives the same new mutation from both father and mother. The probability of such an event is so negligible that the entire population of the Earth is not enough to realize it.

It also follows from this that the repeated occurrence of a mutation in the same family is almost impossible. Therefore, if healthy parents have a sick child with a dominant mutation, then their other children, that is, the patient’s brothers and sisters, should be healthy. However, for the offspring of a sick child, the risk of inheriting the disease will be 50% in accordance with classical rules.

Are there deviations from the usual rules of inheritance and what are they associated with?

Yes, there are. As an exception - sometimes only due to its rarity, such as the appearance of women with hemophilia. They occur more often, but in any case, deviations are caused by complex and numerous relationships between genes in the body and their interaction with environment. In fact, exceptions reflect the same fundamental laws of genetics, but at a more complex level.

For example, many dominantly inherited diseases are characterized by strong variability in their severity, to the point that sometimes the symptoms of the disease in the carrier of the pathological gene may be completely absent. This phenomenon is called incomplete gene penetrance. Therefore, in the pedigrees of families with dominant diseases, so-called skipping generations are sometimes encountered, when known carriers of the gene, having both sick ancestors and sick descendants, are practically healthy.

In some cases, a more thorough examination of such carriers reveals, although minimal, erased, but quite definite manifestations. But it also happens that the methods at our disposal fail to detect any manifestations of a pathological gene, despite clear genetic evidence that a particular person has it.

The reasons for this phenomenon have not yet been sufficiently studied. It is believed that the harmful effect of a mutant gene can be modified and compensated by other genes or environmental factors, but the specific mechanisms of such modification and compensation in certain diseases are unclear.

It also happens that in some families, recessive diseases are passed on for several generations in a row so that they can be confused with dominant ones. If patients marry carriers of the gene for the same disease, then half of their children also inherit a “double dose” of the gene - a condition necessary for the disease to manifest itself. The same thing can happen in subsequent generations, although such “casuistry” occurs only in multiple consanguineous marriages.

Finally, the division of traits into dominant and recessive is not absolute. Sometimes this division is simply arbitrary. The same gene can be considered dominant in some cases, and recessive in others.

Using subtle research methods, it is often possible to recognize the effect of a recessive gene in a heterozygous state, even in completely healthy carriers. For example, the sickle cell hemoglobin gene in a heterozygous state causes the sickle-shaped red blood cells, which does not affect human health, but in a homozygous state it leads to a serious disease - sickle cell anemia.

What is the difference between gene and chromosomal mutations.
What are chromosomal diseases?

Chromosomes are carriers of genetic information at a more complex - cellular level of organization. Hereditary diseases can also be caused by chromosomal defects that arise during the formation of germ cells.

Each chromosome contains its own set of genes, located in a strict linear sequence, that is, certain genes are located not only in the same chromosomes for all people, but also in the same sections of these chromosomes.

Normal cells of the body contain a strictly defined number of paired chromosomes (hence the pairing of the genes they contain). In humans, in each cell, except the sex cells, there are 23 pairs (46) of chromosomes. Sex cells (eggs and sperm) contain 23 unpaired chromosomes - a single set of chromosomes and genes, since paired chromosomes separate during cell division. During fertilization, when the sperm and egg merge, a fetus - an embryo - develops from one cell (now with a complete double set of chromosomes and genes).

But the formation of germ cells sometimes occurs with chromosomal “errors”. These are mutations that lead to changes in the number or structure of chromosomes in a cell. This is why a fertilized egg may contain an excess or deficiency of chromosomal material compared to the norm. Obviously, such a chromosomal imbalance leads to gross disturbances in fetal development. This manifests itself in the form of spontaneous miscarriages and stillbirths, hereditary diseases, and syndromes called chromosomal.

The most famous example of a chromosomal disease is Down's disease (trisomy - the appearance of an extra 21st chromosome). Symptoms of this disease are easily identified by the appearance of the child. This includes a fold of skin in the inner corners of the eyes, which gives the face a Mongoloid appearance, a large tongue, short and thick fingers; upon careful examination, such children also have heart defects, vision and hearing defects, and mental retardation.

Fortunately, the likelihood of this disease and many other chromosomal abnormalities recurring in a family is low: in the vast majority of cases they are caused by random mutations. In addition, it is known that random chromosomal mutations occur more often at the end of the childbearing period.

Thus, as the age of mothers increases, the likelihood of a chromosomal error during egg maturation also increases, and therefore, such women have an increased risk of having a child with chromosomal abnormalities. If the overall incidence of Down syndrome among all newborn children is approximately 1:650, then for the offspring of young mothers (25 years and younger) it is significantly lower (less than 1:1000). The individual risk reaches an average level by the age of 30, it is higher by the age of 38 - 0.5% (1:200), and by the age of 39 - 1% (1:100), and at the age of over 40 it increases to 2- 3%.

Could there be healthy people having chromosomal abnormalities?

Yes, they can with some types of chromosomal mutations, when it is not the number, but the structure of chromosomes that changes. The fact is that structural rearrangements at the initial moment of their appearance may turn out to be balanced - not accompanied by an excess or deficiency of chromosomal material.

For example, two unpaired chromosomes can exchange their sections carrying different genes if, during chromosome breaks, which are sometimes observed during cell division, their ends become sticky and stick together with free fragments of other chromosomes. As a result of such exchanges (translocations), the number of chromosomes in the cell is maintained, but this is how new chromosomes arise in which the principle of strict gene pairing is violated.

Another type of translocation is the gluing of two almost entire chromosomes with their “sticky” ends, resulting in total number chromosomes are reduced by one, although no loss of chromosomal material occurs. A person who is a carrier of such a translocation is completely healthy, but the balanced structural rearrangements he has are no longer accidental, but quite naturally lead to chromosomal imbalance in his offspring, since a significant part of the germ cells of carriers of such translocations have excess or, conversely, insufficient chromosomal material.

Sometimes such carriers cannot have healthy children at all (however, such situations are extremely rare). For example, in carriers of a similar chromosomal anomaly - translocation between two identical chromosomes (say, fusion of the ends of the same 21st pair), 50% of eggs or sperm (depending on the sex of the carrier) contain 23 chromosomes, including a double one, and the remaining 50% contain one chromosome less than expected. During fertilization, cells with a double chromosome will receive another, 21st chromosome, and as a result, children with Down syndrome will be born. Cells with the missing 21st chromosome during fertilization give rise to a non-viable fetus, which spontaneously aborts in the first half of pregnancy.

Carriers of other types of translocations can also have healthy offspring. However, there is a risk of chromosomal imbalance, leading to severe developmental pathology in the offspring. This risk for the offspring of carriers of structural rearrangements is significantly higher than the risk of chromosomal abnormalities resulting from random new mutations.

In addition to translocations, there are other types of structural rearrangements of chromosomes that lead to similar negative consequences. Fortunately, inheritance of chromosomal abnormalities with a high risk of pathology is much less common in life than random chromosomal mutations. The ratio of cases of chromosomal diseases among their mutant and hereditary forms is approximately 95% and 5%, respectively.

How many hereditary diseases are already known?
Is their number increasing or decreasing in human history?

Based on general biological concepts, one would expect an approximate correspondence between the number of chromosomes in the body and the number of chromosomal diseases (and similarly between the number of genes and gene diseases). Indeed, several dozen chromosomal abnormalities with specific characteristics are currently known. clinical symptoms(which actually exceeds the number of chromosomes, because different quantitative and structural changes in the same chromosome cause different diseases).

The number of known diseases caused by mutations of single genes (at the molecular level) is much larger and exceeds 2000. It is estimated that the number of genes on all human chromosomes is much greater. Many of them are not unique, since they are presented in the form of multiple repeating copies on different chromosomes. In addition, many mutations may not manifest themselves as diseases, but lead to embryonic death of the fetus. So the number of gene diseases approximately corresponds to the genetic structure of the organism.

With the development of medical genetic research throughout the world, the number of known hereditary diseases is gradually increasing, and many of them, which have become classic, have been known to people for a very long time. Now in the genetic literature there is a peculiar boom in publications about supposedly new cases and forms of hereditary diseases and syndromes, many of which are usually named after their discoverers.

Every few years, the famous American geneticist Victor McKusick publishes catalogs of hereditary traits and human diseases, compiled on the basis of computer analysis of world literature data. And each time, each subsequent edition differs from the previous one by an increasing number of such diseases. Obviously, this trend will continue, but it rather reflects an improvement in the recognition of hereditary diseases and more careful attention to them, rather than a real increase in their number in the process of evolution.

mutation) - change in the amount or structure of DNA of a given organism. With a point mutation (or gene mutation), any one gene undergoes such a change; With a chromosomal mutation, the structure or number of chromosomes changes. All types of mutations are quite rare and can occur spontaneously or under the influence of any external agents (mutagens). If the mutation occurs in developing sex cells (gametes), it can be inherited. Mutations in any other cells (somatic mutations) are usually not inherited.

MUTATION

An abrupt change in genetic material caused by factors other than normal Mendelian recombination. Mutations become part of the genetic material (that is, they are genotypic), although their effect may not be evident in the phenotype of an individual organism. Most mutations affect individual genes, but there are also global chromosomal changes affecting many genes. A mutation can also occur in the cell body (called a somatic mutation), then it is transmitted through mitosis of that cell. In terms of the adaptive value of a mutation for an individual organism, the results are very random; their role in evolution is mediated by the process of natural selection. Generally speaking, large (macro) mutations are harmful to the organism, and therefore they are not passed on; small (micro) mutations, according to the standard point of view, are the very “essence” of evolution.

Mutation

sudden natural or artificially caused changes in the carriers of hereditary information of the body, not associated with the process of normal redistribution (recombination) of genes. The ability for M. is inherent in all plant and animal organisms and determines one of the two main forms of hereditary variability - mutational variability. There are three types of mutations: gene, chromosomal and genomic.

Mutation

lat. mutatio - change, change) is an abrupt and persistent change in genetic material caused by factors other than Mendelian gene recombinations considered normal. They are distinguished: 1. gametic mutations (occurring in generative, germ cells); 2. somatic mutations (occurring in somatic cells of the body). Depending on the nature of the changes in the genetic apparatus, mutations are further divided into: 3. genomic mutations (for example, diploidy, that is, doubling of the cell genome); 4. chromosomal mutations (for example, trisomy, that is, the appearance of one additional chromosome to the normal two); 5. gene mutations (for example, a change in the structure of one gene, several genes at the same time); 6. mutations of genes localized outside the cell nucleus are called cytoplasmic. Most known mutations affect individual genes; other mutations are less common. The role of mutations in evolution is mediated by the process of natural selection. The vast majority of mutations are destructive, disrupting the viability and preventing the evolution of biological species. See Darwinism.