University of Chicago alumnus Dr. Josiah Zayner has created a set of tools and materials that allow CRISPR to edit the genome at home. According to the scientist, an inexpensive set shows that today, intervention in DNA is a common craft, and not an art with an unpredictable result. The scientist himself willingly demonstrates this idea: in his apartment there are many Petri dishes with genetically modified bacteria created in the kitchen using his own kit.

Biologist Josiah Zayner offers a new approach to popularizing the most advanced part of biological science

The CRISPR genome editing tool was invented three years ago and is a simple, fast and precise way to manipulate DNA. However, until now, CRISPR has been used only by qualified specialists in specialized laboratories.

CRISPR technique allows you to edit the genome even in the kitchen

Josiah Zainer was the first to bring to market a simplified and accessible CRISPR toolkit for genome intervention. This is a provocative initiative, because today the way of life and thinking of society is largely shaped by terrorism. As a result, genetic modification of bacteria at home is associated in most cases with the development of lethal strains for bioterrorists.

Scientists also fear that non-professionals may accidentally create super strains of microorganisms that are resistant to antibiotics. Even if such bacteria and fungi appear to be harmless to humans, they can cause unpredictable changes in the environment.

Gene modifications in the kit are safe and allow only minor changes in the external parameters of microorganisms, such as their color

However, according to Zainer, his kit contains only harmless bacteria and yeasts that cannot survive in a harsh environment and do not live long. Gene modification using kit tools allows only minor changes in their properties, such as color or smell.

A kit for home experiments in genetic engineering costs $120

Josiah Zayner believes that through his recruitment, many talented and curious people can be of great help to biology. Interest in genetic engineering is of great value to science, so a cheap Zayner kit can play an even greater role in the history of biology than a few expensive state-of-the-art laboratories.

It should be noted that crowdfunding brought Zayner's project more than $55,000 - 333% more than the developer of the home gene editing kit had planned.

Mutations (from Latin mutatio - to change) are structural changes in genes that are inherited.

Large mutations (genomic rearrangements) are accompanied by the loss or change of relatively large sections of the genome; such mutations are, as a rule, irreversible.

Small (point) mutations are associated with the loss or addition of individual DNA nucleotides. In this case, only a small number of features change. Such altered bacteria can completely return to their original state (revert).

Bacteria with altered traits are called mutants. Factors that cause the formation of mutants are called mutagens.

Bacterial mutations are divided into spontaneous and induced. Spontaneous (spontaneous) mutations occur under the influence of uncontrolled factors, that is, without the intervention of the experimenter. Induced (targeted) mutations appear as a result of treatment of microorganisms with special mutagens (chemicals, radiation, temperature, and

As a result of bacterial mutations, the following can be noted: a) a change in morphological properties b) a change in cultural properties c) the emergence of resistance to drugs in microorganisms d) a loss of the ability to synthesize amino acids, utilize carbohydrates and other nutrients e) a weakening of pathogenic properties, etc.

If a mutation leads to the fact that mutagenic cells acquire advantages over other cells of the population, then a population of mutant cells is formed and all acquired properties are inherited. If the mutation does not give the cell advantages, then the mutant cells, as a rule, die.

Transformation. Cells that are able to accept the DNA of another cell during transformation are called competent.

Transduction is the transfer of genetic information (DNA) from a donor bacterium to a recipient bacterium with the participation of a bacteriophage. Transducing properties are mainly temperate phages. Reproducing in a bacterial cell, phages incorporate a part of bacterial DNA into their DNA and transfer it to the recipient.

There are three types of transduction: general, specific, and abortive.

1 . General transduction is the transfer of different genes located on different parts of the bacterial chromosome.

At the same time, donor bacteria can transfer various characteristics and properties to the recipient - the ability to form new enzymes, resistance to drugs, etc.

2. Specific transduction is the transfer by the phage of only some specific genes localized in special regions of the bacterial chromosome. In this case, only certain characteristics and properties are transferred.

3. Abortive transduction - transfer by a phage of one fragment of the donor's chromosome. Usually, this fragment is not included in the chromosome of the recipient cell, but circulates in the cytoplasm. When the recipient cell divides, this fragment is transferred only to one of the two daughter cells, and the second cell receives the unchanged chromosome of the recipient.

With the help of transducing phages, a number of properties can be transferred from one cell to another, such as the ability to form toxin, spores, flagella, produce additional enzymes, drug resistance, etc.

Conjugation is the transfer of genetic material from one bacterium to another by direct cell contact. Cells that transfer genetic material are called donors, and those that receive it are called recipients. This process is one-sided - from the donor cell to the recipient cell.

Donor bacteria are designated F+ (male type) and recipient bacteria F- (female type). With close approach of F + and F - cells, a cytoplasmic bridge appears between them. The formation of the bridge is controlled by factor F (from the English. Fertility - fertility). This factor contains the genes responsible for the formation of genital villi (sex pili). Only those cells that contain factor F can perform the donor function. The recipient cells are deprived of this factor. When crossing, the F factor is transferred from the donor cell to the recipient. Having received the F factor, the female cell itself becomes a donor (F +).

The conjugation process can be interrupted mechanically, for example by shaking. In this case, the recipient receives incomplete information contained in the DNA.

Conjugation, like other types of recombination, can occur not only between bacteria of the same species, but also between bacteria of different species. In these cases, recombination is called interspecific.

Plasmids are relatively small extrachromosomal DNA molecules of a bacterial cell. They are located in the cytoplasm and have a circular structure. Plasmids contain several genes that function independently of genes contained in chromosomal DNA.

Prophages that cause a number of inherited changes in a lysogenic cell, for example, the ability to form a toxin (see transduction).

F-factor, which is in an autonomous state and takes part in the process of conjugation (see conjugation).

R-factor, which gives the cell resistance to drugs (for the first time, the R-factor was isolated from Escherichia coli, then from Shigella). Studies have shown that the R factor can be removed from the cell, which is generally characteristic of plasmids.

The K-factor has intraspecific, interspecific and even intergeneric transmissibility, which can cause the formation of difficult-to-diagnose atypical strains.

Bacteriocinogenic factors (col-factors), which were first discovered in the culture of Escherichia coli (E. coli), in connection with which they are called colicins. Later, they were also found in other bacteria: vibrio cholerae - vibriocins, staphylococci - staphylocins, etc.

Co l -factor is a small autonomous plasmid that determines the synthesis of protein substances capable of causing the death of bacteria of its own species or a closely related one. Bacteriocins are adsorbed on the surface of sensitive cells and cause metabolic disorders, which leads to cell death.

Under natural conditions, only a few cells in a population (1 per 1000) spontaneously produce colicin. However, under certain influences on the culture (treatment of bacteria with UV rays), the number of colicin-producing cells increases.

PRACTICAL SIGNIFICANCE OF THE VARIABILITY OF MICROCORAHINES

Even Pasteur artificially obtained irreversible changes in the pathogens of rabies and anthrax and prepared vaccines that protect against these diseases. Further research in the field of genetics and variability of microorganisms made it possible to obtain a large number of bacterial and viral strains used to obtain vaccines.

The results of the study of the genetics of microorganisms were successfully used to elucidate the patterns of heredity in higher organisms.

A new branch of genetics, genetic engineering, is also of great scientific and practical importance.

Genetic engineering methods make it possible to change the structure of genes and include genes of other organisms responsible for the synthesis of important and necessary substances into the bacterial chromosome. As a result, microorganisms become producers of such substances, the production of which by chemical means is a very difficult and sometimes even impossible task. In this way, such medicines as insulin, interferon, etc. are currently obtained. Using mutagenic factors and selection, mutants-producers of antibiotics were obtained, which are 100-1000 times more active than the original ones.

9. Genetics of immunity

Genetic determination of the immune response of the organism of higher animals

Mechanism of synthesis of monospecific antibodies and immune memory

The heritability of the level of the body's immune response and the possibility of selecting animals for resistance to infections.

Immunity is the body's immunity to infectious agents and genetically alien substances of an antigenic nature. The main function of immunity is the immunological supervision of the internal constancy (homeostasis) of the body.

The consequence of this function is the recognition and then blocking, neutralization or destruction of genetically alien substances (viruses, bacteria, cancer cells, etc.). The body's immune system, the totality of all lymphoid cells (a specific protection factor), is responsible for maintaining a genetically determined biological individuality. Nonspecific protective factors include skin and mucous membranes. The immune response, or immunological reactivity, is a form of body reactions to foreign substances (antigens). The main function of antibodies is their ability to enter into a rapid reaction with the antigen in the form of a reaction of glutination, precipitation, lysis, neutralization.

10. Blood groups and biochemical polymorphism.

The concept of blood groups

Heritability of blood types

Practical application of blood groups in animal husbandry

Polymorphic protein systems and their relationship with animal productivity

Methods for determining blood groups and polymorphic protein systems.

Blood groups were discovered in 1900 (in humans) and explained in 1924. And in 1936, the term immunogenetics was used. Within the species, individuals differ in a number of chemical, genetically determined traits that can be detected immunogenetically in the form of antigens (genetically alien substances, when introduced into the body, cause immunogenetic reactions). Antibodies are immunoglobulins (proteins) that form in the body under the influence of antigens; differences in blood grouping are determined by antigens located on the surface of red blood cells. Antigenic factors are sometimes called blood factors, the sum of all blood types of one individual is called the blood type. After the birth of the blood group in animals does not change. Genetic systems of blood groups and antigens are denoted by uppercase and lowercase letters - A, B, C, etc. There are many antigens, so they write with the symbols A, B, C, and with subscripts A1, A2, etc.

Home | About us | Feedback

GENOTYPICAL (HERITABLE) VARIABILITY

Genotypic variability can arise as a result of mutations and genetic recombinations.

Mutations (from Latin mutatio - change) are inherited structural changes in genes.

Large mutations (genomic rearrangements) are accompanied by the loss or change of relatively large sections of the genome; such mutations are usually irreversible.

Small (point) mutations are associated with the loss or addition of individual DNA bases. In this case, only a small number of features change. Such altered bacteria can completely return to their original state (revert).

Bacteria with altered traits are called mutants. Factors that cause the formation of mutants are called mutagens.

Bacterial mutations are divided into spontaneous and induced. Spontaneous (spontaneous) mutations occur under the influence of uncontrolled factors, i.e. without the intervention of the experimenter. Induced (directed) mutations appear as a result of the treatment of microorganisms with special mutagens (chemicals, radiation, temperature, etc.).

Bacterial mutations can result in:

a) change in morphological properties

b) change in cultural properties

c) the emergence of resistance to drugs in microorganisms

d) loss of ability to synthesize amino acids, utilize carbohydrates and other nutrients

e) weakening of pathogenic properties, etc.

If a mutation leads to the fact that mutagenic cells acquire advantages over other cells of the population, then a population of mutant cells is formed, and all acquired properties are inherited. If the mutation does not give the cell advantages, then the mutant cells, as a rule, die. genetic recombination. Transformation. Cells that are able to accept the DNA of another cell during transformation are called competent. The state of competence often coincides with the logarithmic growth phase.

Transduction is the transfer of genetic information from a donor bacterium to a recipient bacterium with the participation of a bacteriophage. Transducing properties are mainly temperate phages. Reproducing in a bacterial cell, phages incorporate a part of bacterial DNA into their DNA and transfer it to the recipient. There are three types of transduction: general, specific and abortive.

1. General transduction is the transfer of various genes located on different parts of the bacterial chromosome. At the same time, donor bacteria can transfer various characteristics and properties to the recipient - the ability to form new enzymes, resistance to drugs, etc.

2. Specific transduction is a transfer
phage only some specific genes localized in special regions of the bacterial chromosome. In this case, only certain characteristics and properties are transferred.

3. Abortive transduction - transfer by a phage of a single enzyme of the donor chromosome. Usually, this fragment is not included in the chromosome of the recipient cell, but circulates in the cytoplasm. When the recipient cell divides, this fragment is transferred only to one of the two daughter cells, and the second cell receives the unchanged chromosome of the recipient.

With the help of transducing phages, a whole range of properties can be transferred from one cell to another, such as the ability to form toxin, spores, flagella, produce additional enzymes, drug resistance, etc.

Conjugation is the transfer of genetic material from one bacterium to another through direct cell contact. Cells that donate genetic material are called donors, and those that receive it are called recipients. This process is one-sided - from the donor cell to the recipient cell.

Donor bacteria are designated F+ (male type) and recipient bacteria are designated F- (female type). When F+ and F- cells come close together, a cytoplasmic bridge appears between them. The formation of the bridge is controlled by factor F (from the English fertility - fertility). This factor contains the genes responsible for the formation of genital villi (sex-pili). The function of a donor can only be performed by those cells that contain factor F. The recipient cells are deprived of this factor. When crossing, the F factor is transferred from the donor cell to the recipient. Having received the F factor, the female cell itself becomes a donor (F +).

The conjugation process can be interrupted mechanically, for example by shaking. In this case, the recipient receives incomplete information contained in the DNA.

The transfer of genetic information by conjugation is best studied in Enterobacteriaceae.

Conjugation, like other types of recombination, can be carried out not only between bacteria of the same species, but also between bacteria of different species. In these cases, recombination is called interspecific.

Genotypic variability is inherited

Plasmids are relatively small extrachromosomal DNA molecules of a bacterial cell. They are located in the cytoplasm and have a circular structure. The plasmids contain several genes that function independently of the genes contained in the chromosomal DNA.

Fig.54 Plasmids (extrachromosomal DNA molecules)

A typical feature of plasmids is their ability to self-reproduce (replicate).

They can also move from one cell to another and include new genes from the environment. Plasmids include:

Prophages. causing a number of changes in the lysogenic cell that are inherited, for example, the ability to form a toxin (see transduction). F-factor, which is in an autonomous state and takes part in the conjugation process (see conjugation).

R-factor, which gives the cell resistance to drugs (for the first time, the R-factor was isolated from Escherichia coli, then from Shigella). Studies have shown that the R-factor can be removed from the cell, which is generally characteristic of plasmids.

The R-factor has intraspecific, interspecific and even intergeneric transmissibility, which can cause the formation of difficult-to-diagnose atypical strains.

Bacteriocinogenic factors (col-factors), which were first discovered in the culture of Escherichia coli (E. coli), in connection with which they are called colicins. Later they were also found in other bacteria: vibrio cholerae - vibriocins, staphylococci - staphylocins, etc.

Col-factor is a small autonomous plasmid that determines the synthesis of protein substances capable of causing the death of bacteria of its own species or a closely related one. Bacteriocins are adsorbed on the surface of sensitive cells and cause metabolic disorders, which leads to cell death.

Under natural conditions, only a few cells in a population (1 per 1000) spontaneously produce colicin. However, under certain influences on the culture (treatment of bacteria with UV rays), the number of colicin-producing cells increases.

Changes in functional genes

For mutated cells, mutations can be somatic (for example, different eye colors in one person) and generative (or gametic). Generative mutations are passed on to offspring, somatic mutations are manifested in the individual itself. They are inherited only through vegetative propagation.

According to the outcome (value) for the organism, mutations are distinguished positive, neutral and negative. Positive mutations are rare. They increase the viability of the organism and are important for evolution (for example, mutations leading to the appearance of a four-chambered heart during the evolution of chordates). Neutral mutations practically do not affect vital processes (for example, mutations that lead to the presence of freckles). Negative mutations are divided into semi-lethal and lethal. Semi-lethal mutations reduce the viability of the organism, shorten its lifespan (for example, mutations leading to Down's disease). Lethal mutations cause
death of the organism before birth or at the time of birth (for example, mutations leading to the absence of a brain).

By changing the phenotype, mutations are morphological (for example, reduced eyeballs, six fingers on the hand) and biochemical (for example, albinism, hemophilia).

By changing the genotype, genomic, chromosomal and gene mutations are distinguished.

Genomic mutations are a change in the number of chromosomes under the influence of environmental factors. Haploidy - a set of chromosomes 1n. In nature, it is found in drones (male) bees. The viability of such organisms is reduced, since they have all the recessive genes.

Polyploidy - an increase in the haploid set of chromosomes (3n, 4n, 5n). Polyploidy is used in crop production. It leads to increased productivity. For humans, haploidy and polyploidy are lethal mutations.

Aneuploidy is a change in the number of chromosomes in separate pairs (2n±1, 2n±2, and so on).

Trisomy. for example, if an X chromosome is added to a pair of sex chromosomes in a female body, trisomy X syndrome develops (47, XXX), if it is added to the sex chromosomes of a male body, Klinefelter syndrome develops (47, XXI). Monosomy. the absence of one chromosome in a pair - 45, X0 - Shereshevsky-Turner syndrome. Nulisomy. the absence of a pair of homologous chromosomes (for humans - a lethal mutation).

Chromosomal mutations (or chromosomal aberrations) are changes in the structure of chromosomes (interchromosomal or intrachromosomal). Rearrangements within one chromosome are called inversions, shortages (deficiencies and deletions), duplications. Interchromosomal rearrangements are called translocations.

Examples: deletion - cat's cry syndrome in humans duplication - the appearance of striped eyes in Drosophila inversion - a change in the order of genes.

Translocations can be: reciprocal - two chromosomes exchange segments non-reciprocal - segments of one chromosome are transferred to another Robertsonian - two acrocentric chromosomes are connected by their centromeric regions.

Deficiencies and duplications always manifest themselves phenotypically as the set of genes changes. Inversions and translocations do not always appear. In these cases, the conjugation of homologous chromosomes becomes more difficult and the distribution of genetic material between daughter cells is disrupted.

Gene mutations are called point mutations, or transgenerations. They are associated with changes in the structure of genes and cause the development of metabolic diseases (their frequency is 2-4%).

Changes in structural genes.

1. A frameshift occurs when one or more pairs of nucleotides are dropped or inserted into a DNA molecule.

2. Transition - a mutation in which a purine base is replaced by a purine base or a pyrimidine base by a pyrimidine base (A G or C T). This substitution results in a codon change.

3. Transversion - replacement of a purine base with a pyrimidine base or a pyrimidine base with a purine base (A C G T) - leads to a change in codons. Changing the meaning of codons leads to miscension mutations. If nonsense codons (UAA, UAG, UGA) are formed, they cause nonsense mutations. These codons do not define amino acids, but are terminators - they determine the end of information reading.

1. The repressor protein has been changed, it does not fit the operator gene. In this case, structural genes are not switched off and work constantly.

2. The repressor protein tightly attaches to the operator gene and is not "removed" by the inductor. Structural genes do not work all the time.

3. Violation of the alternation of the processes of repression and induction. If the inducer is absent, the specific protein is synthesized; in the presence of the inducer, it is not synthesized. Such disturbances in the work of transcriptons are observed with mutations in the gene-regulator or gene-operator.

Currently, about 5,000 metabolic diseases have been described, which are caused by gene mutations. Examples of them can be phenylketonuria, albinism, galactosemia, various hemophilias, sickle cell anemia, achondroplasia, etc.

In most cases, gene mutations manifest themselves phenotypically.

Heredity and variability. Chromosomal theory of heredity

Heredity is the most important feature of living organisms, which consists in the ability to transfer the properties and functions of parents to their descendants. This transmission is carried out with the help of genes.

A gene is a unit of storage, transmission and realization of hereditary information. A gene is a specific section of a DNA molecule, in the structure of which the structure of a certain polypeptide (protein) is encoded. Probably, many DNA regions do not encode proteins, but perform regulatory functions. In any case, in the structure of the human genome, only about 2% of DNA are sequences on the basis of which messenger RNA is synthesized (transcription process), which then determines the amino acid sequence during protein synthesis (translation process). It is currently believed that there are about 30,000 genes in the human genome.

Genes are located on chromosomes, which are located in the nuclei of cells and are giant DNA molecules.

The chromosome theory of heredity was formulated in 1902 by Setton and Boveri. According to this theory, chromosomes are carriers of genetic information that determines the hereditary properties of an organism. In humans, each cell has 46 chromosomes, divided into 23 pairs. Chromosomes that form a pair are called homologous.

Sex cells (gametes) are formed using a special type of division - meiosis. As a result of meiosis, only one homologous chromosome from each pair remains in each germ cell, i.e. 23 chromosomes. Such a single set of chromosomes is called haploid. At fertilization, when the male and female sex cells merge and a zygote is formed, the double set, which is called diploid, is restored. In the zygote of the organism that develops from it, one chromosome from each nara is received from the paternal organism, the other from the maternal one.

A genotype is a set of genes received by an organism from its parents.

Another phenomenon that genetics studies is variability. Variability is understood as the ability of organisms to acquire new features - differences within a species. There are two types of change:
- hereditary
- modification (non-hereditary).

Hereditary variability is a form of variability caused by changes in the genotype, which may be associated with mutational or combinative variability.

mutational variability.
Genes undergo changes from time to time, which are called mutations. These changes are random and appear spontaneously. The causes of mutations can be very diverse. There are a number of factors that increase the likelihood of a mutation occurring. This may be exposure to certain chemicals, radiation, temperature, etc. Mutations can be caused by these means, but the random nature of their occurrence remains, and it is impossible to predict the appearance of a particular mutation.

The resulting mutations are transmitted to descendants, that is, they determine hereditary variability, which is associated with where the mutation occurred. If a mutation occurs in a germ cell, then it has the opportunity to be transmitted to descendants, i.e. be inherited. If the mutation occurred in a somatic cell, then it is transmitted only to those of them that arise from this somatic cell. Such mutations are called somatic, they are not inherited.

There are several main types of mutations.
- Gene mutations, in which changes occur at the level of individual genes, i.e. sections of the DNA molecule. This can be a waste of nucleotides, the replacement of one base with another, a rearrangement of nucleotides, or the addition of new ones.
- Chromosomal mutations associated with a violation of the structure of chromosomes lead to serious changes that can be detected using a microscope. Such mutations include loss of chromosome sections (deletions), addition of sections, rotation of a chromosome section by 180°, and the appearance of repeats.
- Genomic mutations are caused by a change in the number of chromosomes. Extra homologous chromosomes may appear: in the chromosome set, in place of two homologous chromosomes, there are three trisomy. In the case of monosomy, there is a loss of one chromosome from a pair. With polyploidy, a multiple increase in the genome occurs. Another variant of genomic mutation is haploidy, in which only one chromosome from each pair remains.

The frequency of mutations is affected, as already mentioned, by a variety of factors. When a number of genomic mutations occur, the age of the mother, in particular, is of great importance.

Combination variability.
This type of variability is determined by the nature of the sexual process. With combinative variability, new genotypes arise due to new combinations of genes. This type of variability is manifested already at the stage of formation of germ cells. As already mentioned, each sex cell (gamete) contains only one homologous chromosome from each pair. Chromosomes enter the gamete randomly, so the germ cells of one person can differ quite a lot in the set of genes in the chromosomes. An even more important stage for the emergence of combinative variability is fertilization, after which 50% of the genes of the newly emerged organism are inherited from one parent, and 50% from the other.

Modification variability is not associated with changes in the genotype, but is caused by the influence of the environment on the developing organism.

The presence of modification variability is very important for understanding the essence of inheritance. Traits are not inherited. You can take organisms with exactly the same genotype, for example, grow cuttings from the same plant, but place them in different conditions (light, humidity, mineral nutrition) and get quite different plants with different traits (growth, yield, leaf shape). and so on.). To describe the actually formed signs of an organism, the concept of "phenotype" is used.

The phenotype is the whole complex of actually occurring signs of an organism, which is formed as a result of the interaction of the genotype and environmental influences during the development of the organism. Thus, the essence of inheritance lies not in the inheritance of a trait, but in the ability of the genotype, as a result of interaction with developmental conditions, to give a certain phenotype.

Since modification variability is not associated with changes in the genotype, modifications are not inherited. Usually this position is for some reason difficult to accept. It seems that if, say, parents train for several generations in lifting weights and have developed muscles, then these properties must be passed on to children. Meanwhile, this is a typical modification, and training is the influence of the environment that influenced the development of the trait. No changes in the genotype occur during modification, and the traits acquired as a result of modification are not inherited. Darwin called this kind of variation - non-hereditary.

To characterize the limits of modification variability, the concept of the reaction norm is used. Some traits in a person cannot be changed due to environmental influences, such as blood type, gender, eye color. Others, on the contrary, are very sensitive to the effects of the environment. For example, as a result of prolonged exposure to the sun, the skin color becomes darker, and the hair lightens. The weight of a person is strongly influenced by dietary habits, illness, the presence of bad habits, stress, lifestyle.

Environmental influences can lead not only to quantitative, but also to qualitative changes in the phenotype. In some species of primrose, at low air temperatures (15-20 C), red flowers appear, but if the plants are placed in a humid environment with a temperature of 30 ° C, then white flowers form.

moreover, although the reaction rate characterizes a non-hereditary form of variability (modification variability), it is also determined by the genotype. This provision is very important: the reaction rate depends on the genotype. The same influence of the environment on the genotype can lead to a strong change in one of its traits and not affect the other in any way.

21. Gene is a functional unit of heredity. Molecular structure of the gene in prokaryotes and eukaryotes. Unique genes and DNA repeats. structural genes. Hypothesis "1 gene - 1 enzyme", its modern interpretation.

A gene is a structural and functional unit of heredity that controls the development of a particular trait or property. The set of genes parents pass on to offspring during reproduction. The term gene was coined in 1909 by the Danish botanist Wilhelm Johansen. The science of genetics is engaged in the study of genes, the founder of which is Gregor Mendel, who in 1865 published the results of his research on the transmission of traits by inheritance when crossing peas. Genes can undergo mutations - random or purposeful changes in the sequence of nucleotides in the DNA chain. Mutations can lead to a change in sequence, and therefore a change in the biological characteristics of a protein or RNA, which, in turn, can result in a general or local altered or abnormal functioning of the organism. Such mutations in some cases are pathogenic, since their result is a disease, or lethal at the embryonic level. However, not all changes in the nucleotide sequence lead to a change in the protein structure (due to the effect of the degeneracy of the genetic code) or to a significant change in the sequence and are not pathogenic. In particular, the human genome is characterized by single nucleotide polymorphisms and copy number variations, such as deletions and duplications, which make up about 1% of the entire human nucleotide sequence. Single nucleotide polymorphisms, in particular, define different alleles of the same gene.

In humans, as a result of a deletion:

Wolf's syndrome - a missing section of the large chromosome 4,

“Cat's cry” syndrome - with a deletion in chromosome 5. Cause: chromosomal mutation loss of a chromosome fragment in the 5th pair.

Manifestation: abnormal development of the larynx, feline-like cries, I in early childhood, lag in physical and mental development.

The monomers that make up each of the DNA chains are complex organic compounds that include nitrogenous bases: adenine (A) or thymine (T) or cytosine (C) or guanine (G), a five-atom sugar-pentose-deoxyribose, named after which and received the name of DNA itself, as well as the residue of phosphoric acid. These compounds are called nucleotides.

The chromosome of any organism, be it a bacterium or a human, contains a long, continuous chain of DNA. along which many genes are located. Different organisms differ dramatically in the amount of DNA that makes up their genomes. In viruses, depending on their size and complexity, the size of the genome ranges from several thousand to hundreds of base pairs. Genes in such simply arranged genomes are located one after another and occupy up to 100% of the length of the corresponding nucleic acid (RNA and DNA). For many viruses, the complete DNA nucleotide sequence has been established. Bacteria have a much larger genome. In Escherichia coli, the only strand of DNA - the bacterial chromosome consists of 4.2x106 (6 degree) base pairs. More than half of this amount consists of structural genes, i.e. genes that code for certain proteins. The rest of the bacterial chromosome consists of nucleotide sequences unable to be transcribed, the function of which is not entirely clear. The vast majority of bacterial genes are unique; present only once in the genome. The exception is the transport and ribosomal RNA genes, which can be repeated dozens of times.

The genome of eukaryotes, especially higher ones, is much larger than the genome of prokaryotes and reaches, as noted, hundreds of millions and billions of base pairs. The number of structural genes in this case does not increase very much. The amount of DNA in the human genome is sufficient for the formation of approximately 2 million structural genes. The actual number available is estimated at 50-100 thousand genes, i.e. 20-40 times smaller than what could be encoded by a genome of this size. Therefore, we have to state the redundancy of the eukaryotic genome. The causes of redundancy are now largely clear: firstly, some genes and nucleotide sequences are repeated many times, secondly, there are many genetic elements in the genome that have a regulatory function, and thirdly, part of the DNA does not contain genes at all.

According to modern concepts, the gene encoding the synthesis of a certain protein in eukaryotes consists of several mandatory elements. First of all, this is an extensive regulatory zone that has a strong influence on the activity of a gene in a particular tissue of the body at a certain stage of its individual development. Next is a promoter directly adjacent to the coding elements of the gene - a DNA sequence up to 80-100 base pairs long, responsible for binding the RNA polymerase that transcribes this gene. Following the promoter lies the structural part of the gene, which contains information about the primary structure of the corresponding protein. This region for most eukaryotic genes is significantly shorter than the regulatory zone, but its length can be measured in thousands of base pairs.

An important feature of eukaryotic genes is their discontinuity. This means that the region of the gene encoding the protein consists of two types of nucleotide sequences. Some - exons - are sections of DNA that carry information about the structure of the protein and are part of the corresponding RNA and protein. Others - introns - do not encode the structure of the protein and are not included in the composition of the mature mRNA molecule, although they are transcribed. The process of cutting out introns - "unnecessary" sections of the RNA molecule and splicing of exons during the formation of mRNA is carried out by special enzymes and is called Splicing (crosslinking, splicing).

The eukaryotic genome is characterized by two main features:

1) Repetition of sequences

2) Separation by composition into various fragments characterized by a specific content of nucleotides

Repeated DNA consists of nucleotide sequences of various lengths and compositions that occur several times in the genome, either in tandem-repeated or dispersed form. DNA sequences that do not repeat are called unique DNA. The size of the portion of the genome occupied by repeating sequences varies widely between taxa. In yeast, it reaches 20%; in mammals, up to 60% of all DNA is repeated. In plants, the percentage of repeated sequences can exceed 80%.

By mutual orientation in the DNA structure, direct, inverted, symmetrical repeats, palindromes, complementary palindromes, etc. are distinguished. In a very wide range, both the length (in the number of bases) of the elementary repeating unit, and the degree of their repetition, and the nature of distribution in the genome vary. the periodicity of DNA repetitions can have a very complex structure, when short repeats are included in longer ones or fringe them, etc. In addition, mirror and inverted repeats can be considered for DNA sequences. The human genome is 94% known. Based on this material, the following conclusion can be drawn - repeats occupy at least 50% of the genome.

STRUCTURAL GENES - genes encoding cellular proteins with enzymatic or structural functions. They also include genes encoding the structure of rRNA and tRNA. There are genes that contain information about the structure of the polypeptide chain, ultimately - structural proteins. Such sequences of nucleotides one gene long are called structural genes. Genes that determine the place, time, duration of the inclusion of structural genes are regulatory genes.

Genes are small in size, although they consist of thousands of base pairs. The presence of a gene is established by the manifestation of the trait of the gene (final product). The general scheme of the structure of the genetic apparatus and its work was proposed in 1961 by Jacob, Monod. They proposed that there is a section of the DNA molecule with a group of structural genes. Adjacent to this group is a 200 bp site, the promoter (the site of adjunction of DNA-dependent RNA polymerase). The operator gene adjoins this site. The name of the whole system is operon. Regulation is carried out by a regulatory gene. As a result, the repressor protein interacts with the operator gene, and the operon begins to work. The substrate interacts with the gene regulators, the operon is blocked. Feedback principle. The expression of the operon is turned on as a whole. 1940 - Beadle and Tatum proposed a hypothesis: 1 gene - 1 enzyme. This hypothesis played an important role - scientists began to consider the final products. It turned out that the hypothesis has limitations, because All enzymes are proteins, but not all proteins are enzymes. As a rule, proteins are oligomers - i.e. exist in a quaternary structure. For example, a tobacco mosaic capsule has over 1200 polypeptides. In eukaryotes, the expression (manifestation) of genes has not been studied. The reason is serious obstacles:

Organization of genetic material in the form of chromosomes

In multicellular organisms, cells are specialized and therefore some of the genes are turned off.

The presence of histone proteins, while prokaryotes have “naked” DNA.

Histone and non-histone proteins are involved in gene expression and are involved in the creation of structure.

22. Classification of genes: structural genes, regulators. Properties of genes (discreteness, stability, lability, polyallelism, specificity, pleiotropy).

Discreteness - immiscibility of genes

Stability - the ability to maintain a structure

Lability - the ability to repeatedly mutate

Multiple allelism - many genes exist in a population in multiple molecular forms

Allelism - in the genotype of diploid organisms, only two forms of the gene

Specificity - each gene encodes a different trait

Pleiotropy - multiple gene effect

Expressivity - the degree of expression of a gene in a trait

Penetrance - the frequency of expression of a gene in the phenotype

Amplification is an increase in the number of copies of a gene.

23. The structure of the gene. Regulation of gene expression in prokaryotes. The operon hypothesis.

Gene expression is the process by which hereditary information from a gene (a sequence of DNA nucleotides) is converted into a functional product - RNA or protein. Gene expression can be regulated at all stages of the process: during transcription, during translation, and at the stage of post-translational modifications of proteins.

Regulation of gene expression allows cells to control their own structure and function and is the basis of cell differentiation, morphogenesis, and adaptation. Gene expression is a substrate for evolutionary change, since control over the timing, location, and amount of expression of one gene can have an impact on the function of other genes in the whole organism. In prokaryotes and eukaryotes, genes are sequences of DNA nucleotides. On the DNA matrix, transcription occurs - the synthesis of complementary RNA. Further, translation occurs on the mRNA matrix - proteins are synthesized. There are genes encoding non-messenger RNA (eg, rRNA, tRNA, small RNA) that are expressed (transcribed) but not translated into proteins.

Studies on E. coli cells made it possible to establish that bacteria have 3 types of enzymes:

constitutive, present in cells in constant quantities, regardless of the metabolic state of the body (for example, glycolysis enzymes)

induced, their concentration under normal conditions is low, but can increase by a factor of 100 or more if, for example, a substrate of such an enzyme is added to the cell culture medium

repressed, i.e. enzymes of metabolic pathways, the synthesis of which stops when the end product of these pathways is added to the growth medium.

Based on genetic studies of the induction of β-galactosidase, which is involved in E. coli cells, in the hydrolytic cleavage of lactose, Francois Jacob and Jacques Monod in 1961 formulated the operon hypothesis, which explained the mechanism of control of protein synthesis in prokaryotes.

In experiments, the operon hypothesis was fully confirmed, and the type of regulation proposed in it was called the control of protein synthesis at the level of transcription, since in this case the change in the rate of protein synthesis is carried out due to a change in the rate of gene transcription, i.e. at the stage of mRNA formation.

In E. coli, as in other prokaryotes, DNA is not separated from the cytoplasm by a nuclear envelope. During transcription, primary transcripts are formed that do not contain introns, and mRNAs are devoid of a "cap" and a poly-A end. Protein synthesis begins before the synthesis of its template ends, i.e. transcription and translation occur almost simultaneously. Based on the size of the genome (4×106 base pairs), each E. coli cell contains information about several thousand proteins. But under normal growth conditions, it synthesizes about 600-800 different proteins, which means that many genes are not transcribed; inactive. Protein genes, whose functions in metabolic processes are closely related, are often grouped together in the genome into structural units (operons). According to the theory of Jacob and Monod, operons are sections of a DNA molecule that contain information about a group of functionally interconnected structural proteins, and a regulatory zone that controls the transcription of these genes. The structural genes of the operon are expressed in concert, or they are all transcribed, in which case the operon is active, or none of the genes is "read", in which case the operon is inactive. When an operon is active and all its genes are transcribed, polycistronic mRNA is synthesized, which serves as a template for the synthesis of all proteins of this operon. Transcription of structural genes depends on the ability of RNA polymerase to attach to a promoter located at the 5' end of the operon before the structural genes.

The binding of RNA polymerase to a promoter depends on the presence of a repressor protein in a region adjacent to the promoter, which is called the "operator". The repressor protein is synthesized in the cell at a constant rate and has an affinity for the operator site. Structurally, the regions of the promoter and operator partially overlap; therefore, the attachment of the repressor protein to the operator creates a steric obstacle to the attachment of RNA polymerase.

Most of the mechanisms of regulation of protein synthesis are aimed at changing the rate of binding of RNA polymerase to the promoter, thus affecting the stage of transcription initiation. Genes involved in the synthesis of regulatory proteins can be removed from the operon whose transcription they control.

In the fifties of the XX century, scientists were faced with a strange phenomenon. They drew attention to the fact that some viruses infect different strains of the same bacteria in different ways. Some strains - for example, E. coli - became infected easily and quickly spread the infection throughout the colony. Others became infected very slowly or were completely resistant to the viruses. But once having adapted to this or that strain, in the future the virus infected it without difficulty.

It took biologists two decades to figure out this selective resistance of bacteria. As it turned out, the ability of certain strains of bacteria to resist viruses - it was called restriction (that is, "restriction") - is due to the presence of special enzymes in them that physically cut the viral DNA.

The peculiarity of these proteins - restriction enzymes - is that they recognize a small and strictly defined DNA sequence. Bacteria "target" restriction enzymes to rare sequences that they themselves avoid in their genes - but which may be present in viral DNA. Different restriction enzymes recognize different sequences.

Each strain of bacteria has a specific arsenal of such enzymes and thus responds to a specific set of "words" in the virus genome. If we imagine that the genome of a virus is the phrase "mom washed the frame", then the virus will not be able to infect a bacterium that recognizes the word "mom", but a bacterium that targets the word "uncle" will be defenseless. If the virus manages to mutate and turn into, say, a “woman washing a frame,” then the first bacterium will also lose its protection.

Why is the discovery of "bacterial immunity" at the very top of the list of the most important achievements of molecular biology? It's not the bacteria themselves, or even the viruses.

Measure a piece of DNA

The scientists who described this mechanism almost immediately drew attention to the most important detail of this process. Restriction enzymes (more precisely, one of the types of these enzymes) are able to cut DNA at a well-defined point. Returning to our analogy, an enzyme that targets the word "mother" in DNA binds to that word and cuts it, for example, between the third and fourth letter.

Thus, for the first time, researchers have the opportunity to “cut” the DNA fragments they need from genomes. With the help of special "gluing" enzymes, the resulting fragments could be stitched together - also in a certain order. With the discovery of restriction enzymes, scientists had all the necessary tools for "assembling" DNA in their hands. Over time, a slightly different metaphor took root to refer to this process - genetic engineering.

Although there are other methods of working with DNA today, the vast majority of biological research of the last twenty or thirty years would not have been possible without restriction enzymes. From transgenic plants to gene therapy, from recombinant insulin to induced stem cells, any work involving genetic manipulation uses this "bacterial weapon".

Know the enemy by sight

The immune system of mammals - including humans - has both innate and acquired defense mechanisms. The innate components of immunity usually react to something in common that unites many enemies of the body at once. For example, innate immunity can recognize bacterial cell wall components that are the same for thousands of different microbes.

Acquired immunity relies on the phenomenon of immunological memory. It recognizes specific components of specific pathogens, "remembering" them for the future. Vaccination is based on this: the immune system “trains” on a killed virus or bacterium, and later, when a living pathogen enters the body, it “recognizes” it and destroys it on the spot.

Innate immunity is a border checkpoint. It protects from everything at once and at the same time from nothing in particular. Acquired immunity is a sniper who knows the enemy by sight. As it turned out in 2012, bacteria have something similar.

If restriction is a bacterial analogue of innate immunity, then the role of acquired immunity in bacteria is performed by a system with a rather cumbersome name CRISPR / Cas9, or "Crisper".

The essence of Crisper's work is as follows. When a bacterium is attacked by a virus, it copies part of the virus's DNA to a special place in its own genome (this "repository" of information about viruses is called CRISPR). Based on these saved "identikit" of the virus, the bacterium then makes an RNA probe capable of recognizing the viral genes and binding to them if the virus tries to infect the bacterium again.

The RNA probe itself is harmless to the virus, but this is where another player comes into play: the Cas9 protein. It is a "scissors" responsible for the destruction of viral genes - like a restriction enzyme. Cas9 grabs onto the RNA probe and, as if on a leash, is delivered to the viral DNA, after which it is given a signal: cut here!

In total, the entire system consists of three bacterial components:

1) DNA storage of "identikit" old viruses;

2) an RNA probe made on the basis of these "identikit images" and capable of identifying a virus by them;

3) protein "scissors" tied to an RNA probe and cutting viral DNA exactly at the point from which the "identikit" was taken last time.

Almost instantly after the discovery of this “bacterial immunity”, everyone forgot about bacteria and their viruses. The scientific literature exploded with enthusiastic articles about the potential of the CRISPR/Cas9 system as a tool for genetic engineering and medicine of the future.

As in the case of restriction enzymes, the Crisper system is able to cut DNA at a strictly defined point. But compared to the "scissors" discovered in the seventies, it has huge advantages.

Restriction enzymes are used by biologists to “mount” DNA exclusively in a test tube: you must first make the desired fragment (for example, a modified gene), and only then introduce it into a cell or organism. "Crisper" can cut DNA on the spot, right in a living cell. This makes it possible not only to manufacture artificially introduced genes, but also to “edit” entire genomes: for example, to remove some genes and insert new ones instead. Until recently, one could only dream of such a thing.

As it became clear over the past year, the CRISPR system is unpretentious and can work in any cell: not only bacterial, but also mouse or human. "Install" it in the desired cell is quite simple. In principle, this can be done even at the level of whole tissues and organisms. In the future, this will make it possible to completely remove defective genes - for example, those that cause cancer - from the adult human genome.

Let's say that the phrase "mom washed the frame" present in your genome causes you to have a painful craving for gender stereotypes. To get rid of this problem, you need a Cas9 protein - always the same - and a pair of RNA probes aimed at the words "mama" and "frame". These probes can be anything - modern methods make it possible to synthesize them in a few hours. There are no restrictions on the number at all: you can “cut” the genome at least at a thousand points at the same time.

Targeting the body

But Crisper's value goes beyond the scissor function. As many authors note, this system is the first tool known to us with which it is possible to organize a "meeting" of a certain protein, a certain RNA and a certain DNA at the same time. This in itself opens up enormous opportunities for science and medicine.

For example, the Cas9 protein can be turned off the "scissor" function, and instead bind to it another protein - say, a gene activator. With the right RNA probe, the resulting pair can be sent to the right place in the genome: for example, to a poorly functioning insulin gene in some diabetics. By organizing the meeting of the activating protein and the disabled gene in this way, it is possible to precisely and finely tune the functioning of the organism.

You can bind not only activators, but anything in general - say, a protein that can replace a defective gene with its “backup copy” from another chromosome. Thus, in the future, it will be possible to cure, for example, Huntington's disease. The main advantage of the CRISPR system in this case is precisely its ability to “send expeditions” to any point in DNA that we can program without much difficulty. What is the task of each particular expedition - is determined only by the imagination of the researchers.

Today it is difficult to say what kind of problems the CRISPR/Cas9 system will be able to solve in a few decades. The global community of geneticists is now reminiscent of a child who was allowed into a huge hall filled to overflowing with toys. The leading scientific journal Science recently published an overview of the latest advances in the field called "The CRISPR Craze" - "Crisper Madness". And yet, it is already obvious now: bacteria and fundamental science have once again given us a technology that will change the world.

In January, there were reports of the birth of the first primates whose genome was successfully modified by the CRISPR/Cas9 system. As a test experiment, the monkeys were introduced with mutations in two genes: one associated with the immune system, and the other responsible for the deposition of fat, which opaquely hints at a possible application of the method to homo sapiens. Perhaps the solution to the problem of obesity by genetic engineering is not such a distant future.

Changing human DNA that is passed on to future generations has long been considered ethically closed and banned in many countries. Scientists report they are using new tools to repair disease genes in human embryos. Although the researchers are using defective embryos and have no intention of implanting them in a woman's uterus, the work is troubling.

A change in the DNA of human eggs, sperm, or embryos is known as a germline change. Many scientists are calling for a moratorium on the revision of clinical embryos, editing the human germ line, and many believe that this type of scientific activity should be banned.

However, editing the DNA of a human embryo may be ethically acceptable to prevent illness in a child, but only in rare cases and with guarantees. These situations can be limited to couples where they both have serious genetic conditions and for whom embryo editing is really the last reasonable option if they want to have a healthy baby.

The danger of deliberately changing genes

Scientists believe that editing a human embryo may be acceptable to prevent a child from inheriting serious genetic diseases, but only if certain safety and ethical criteria are met. For example, a couple cannot have "reasonable alternatives" such as being able to select healthy embryos for in vitro fertilization (IVF) or through prenatal testing and abortion of a fetus with a disease. Another situation that may meet the criteria is if both parents have the same medical condition, such as cystic fibrosis.

The scientists warn of the need for strict government oversight to prevent germline editing from being used for other purposes, such as giving a child desirable, distinctive traits.

By editing genes in patient cells that are not inherited, clinical trials are already underway to fight HIV, hemophilia and leukemia. It is believed that the existing regulatory systems for gene therapy are sufficient to carry out such work.

Genome editing should not be to increase potency, increase muscle strength in a healthy person, or lower cholesterol levels.

Human germline gene editing or human germline modification means the intentional modification of genes that is passed on to children and future generations.

In other words, creation of genetically modified humans. Human germline modification has been considered a taboo subject for many years due to safety and social reasons. It is formally banned in more than 40 countries.

Experiments on the creation of genetically modified people and the science of eugenics

However, in recent years, new methods of genetic engineering have been used to experiment with human embryos. For research, genes and human embryos associated with beta blood disease - thalassemia were used. The experiments were mostly unsuccessful. But gene-editing tools are being developed in labs around the world and are expected to make it easier, cheaper, and more accurate to edit or delete genes than ever before. Modern yet theoretical methods of editing the genome will allow scientists to insert, delete and tweak DNA with positive results. This holds the promise of treating certain diseases, such as sickle cell disease, cystic fibrosis, and certain types of cancer.

Selection in relation to humans - eugenics

Gene editing of human embryos or the direction of eugenics leads to the creation of genetically modified very different people. This causes serious security due to social and ethical issues. They range from the prospect of irreversible harm to the health of future children and generations, to opening doors to new forms of social inequality, discrimination and conflict and a new era of eugenics.

The science of eugenics for human selection came into existence in the middle of the last century as a science of the Nazi direction.

Scientists are not allowed to make changes to human DNA, which is passed on to subsequent generations. Such an innovative step in the science of eugenics should be considered only after additional research, after which changes can be made under severe restrictions. Such work should be prohibited in order to prevent serious illness and disability.

Variation caused by changing genes is also called mutations.

It is a long taboo against making changes in the genes of human sperm, eggs or embryos, because such changes will be inherited by future generations. This is taboo in part because of the fear that mistakes could inadvertently create new artificial diseases that could then become a permanent part of the human gene pool.

Another problem is that this species can be used for genetic modification for non-medical reasons. For example, scientists could theoretically try to create a child constructor in which parents try to select the traits of their children to make them smarter, taller, better athletes, or with other supposedly necessary attributes.

Nothing like this is currently possible. But even the prospect causes fears of scientists to significantly change the course of evolution and the creation of people who are considered genetically improved, to come up with what dystopias of the future, described in films and books.

Any attempt to create babies from sperm, eggs or embryos that have their own DNA and attempt to edit can only be done under very carefully controlled conditions and only to prevent devastating disease.

It can be difficult to further distinguish between using gene editing to prevent or treat a disease and using it to enhance a person's abilities.

For example, if scientists manage to find out that gene changes increase mental abilities to fight off dementia in Alzheimer's disease, then this can be considered preventive medicine. If you simply radically improve the memory of a healthy person, then this is no longer a medical direction.

When is it allowed to change DNA

The ability to edit genes can be used to treat many diseases and possibly even prevent many devastating disorders from occurring in the first place by editing out genetic mutations in the sperm, egg and embryo. Some potential changes could prevent a wide range of diseases, including breast cancer, Tay-Sachs disease, sickle cell anemia, cystic fibrosis, and Huntington's disease.

Clinical trials for gene editing should be allowed if:

• no “reasonable alternative” to prevent “serious illness”
• it has been convincingly proven that genes, when edited, eliminate the cause of the disease
• changes are aimed only at the transformation of such genes that are associated with the usual state of health
• Sufficient preliminary research work has been carried out on the risks and potential health benefits
• continuous, rigorous supervision to study the effect of the procedure on the health and safety of participants, and long-term comprehensive plans
• there is maximum transparency in accordance with patient confidentiality and reassessment of health, social benefits and risks is underway
• there are robust oversight mechanisms in place to prevent the spread of a serious disease or condition.

Proponents of human germline editing argue that it could potentially reduce, or even eliminate, the occurrence of many serious genetic diseases that would reduce human suffering throughout the world. Opponents say that altering human embryos is dangerous and unnatural, and does not take into account the consent of future generations.

Discussion on the change of the human embryo

Let's start with the objection that changing the fetus is unnatural or playing against God.

This argument is based on the premise that natural is inherently good.

But illnesses are natural and people by the millions fall ill and die prematurely - all quite naturally. If we only protected natural beings and natural phenomena, we would not be able to use antibiotics to kill bacteria or otherwise practice medicine or fight drought, famine, pestilence. The health care system is maintained in every developed country and can rightly be described as part of a comprehensive attempt to thwart the course of nature. Which of course is neither good nor bad. Natural substances or natural treatments are better, if they are, of course, possible.

Leads to an important moment in the history of medicine and genome editing and represents promising scientific endeavors for the benefit of all mankind.

Interference with the human genome is permitted only for prophylactic, diagnostic or therapeutic purposes and without modification for offspring.

Rapid progress in the field of genetics, the so-called "designer babies" increases the need for bioethics for a broader public and debate about the power of science. Science is able to genetically modify human embryos in the laboratory to control inherited traits such as appearance and intelligence.

As of now, many countries have signed an international convention banning this kind of gene editing and DNA modification.

Mutation ( lat. mutatio - change) - a persistent transformation of the genotype that occurs under the influence of the external or internal environment.

Genomic mutations - these are mutations that result in the addition or loss of one, several, or complete haploid set of chromosomes. Different types of genomic mutations are called heteroploidy and polyploidy.

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- changes on one or two chromosomes. For example, one extra twenty-first chromosome leads to Down syndrome (while the total number of chromosomes is 47)

26. Change in the number and order of genes (chromosomal rearrangements)

Chromosomal rearrangements(they are also called aberrations) occur in the case of two or more chromosome breaks.

· deletion, or shortage. Lost part of a chromosome.

· duplication, or doubling. One of the sections of the chromosome is presented in the chromosome set more than once.

· Inversion arises as a result of two breaks in one chromosome, but on condition that the internal fragment of the chromosome makes a 180-degree turn, i.e. its polarity is reversed.

The inverted region of the chromosome may or may not include the centromere. In the first case, the inversion is called pericentric(i.e. covering the centromere), and in the second - paracentric(near-centromeric).

Translocations . If the breaks are in two chromosomes, then an exchange of fragments is possible during reunification. With symmetrical reunion, new chromosomes are formed in which the exchange of distal regions of non-homologous chromosomes has occurred. Such translocations are called reciprocal.

A segment of a chromosome can also change its position without reciprocal exchange, remaining in the same chromosome, or being included in some other one. Such non-reciprocal translocations are sometimes called transpositions .

In the case of the connection of two acrocentric chromosomes in the region of their centromeres with the loss of short arms, a centric fusion is observed - Robertsonian translocation.

27. Change in individual genes (gene mutation)

Mutations(from Latin mutatio - change) is a change in genes and chromosomes, phenotypically manifested in a change in the properties and characteristics of organisms.

Gene (point) mutations- these are changes in the number and / or sequence of nucleotides in the DNA structure (insertions, deletions, displacements, substitutions of nucleotides) within individual genes, leading to a change in the quantity or quality of the corresponding protein products.

Transfer of a gene mutation.

It occurs according to the usual laws of heredity. The risk for offspring is more or less great, depending on whether the “sick” gene is dominant or recessive and where it is located - on the normal chromosome or on the sex chromosome. Just keep in mind that if a gene is recessive, the person can pass it on to their offspring.

A typical example is hemophilia - a disease of the blood (a violation of its coagulability). This disease differs in that it is transmitted only by women, but causes disturbances only in men; in other words, a woman who is outwardly healthy can oppose this disease to one of her sons.