Hereditary thrombophilia due to gene polymorphism. Genetic polymorphism, its biological, medical and social aspects

Polymorphism of human populations. Genetic load.

Classification of polymorphism.

Genetic polymorphism human populations.

Genetic load.

Genetic aspects of predisposition to diseases.

Natural selection can:

Stabilize the view;

Lead to new formation of species;

Promote diversity.

Polymorphism– the existence in a single panmix population of two or more sharply different phenotypes. They may be normal or abnormal. Polymorphism is an intrapopulation phenomenon.

Polymorphism happens:

Chromosomal;

Transition;

Balanced.

Genetic polymorphism occurs when a gene is represented by more than one allele. An example is blood group systems.

Chromosomal polymorphism - there are differences between individuals on individual chromosomes. This is the result of chromosomal aberrations. There are differences in heterochromatic regions. If the changes do not have pathological consequences - chromosomal polymorphism, the nature of the mutations is neutral.

Transitional polymorphism is the replacement of one old allele in a population with a new one, which is more useful under given conditions. Humans have a haptoglobin gene - Hp1f, Hp 2fs. The old allele is Hp1f, the new allele is Hp2fs. HP forms a complex with hemoglobin and causes the adhesion of red blood cells in the acute phase of diseases.

Balanced polymorphism occurs when none of the genotypes receives an advantage, and natural selection favors diversity.

All forms of polymorphism are very widespread in nature in populations of all organisms. In populations of organisms that reproduce sexually, there is always polymorphism.

The root "morphism" involves consideration of structure.

Now the term “polymorphism” is understood as any trait that is determined genetically and is not a consequence of phenocopy. Very often there are 2 alternative characters, then they talk about dimorphism. For example, sexual dimorphism.

Until the mid-60s of the twentieth century (more precisely, 1966), mutations with a morphological characteristic were used to study polymorphism. They happen with low frequency, lead to serious changes, and therefore are very noticeable.

Timofeev – Risovsky “on the flower morphs of the Berlin ladybug population...”. 8 types of coloring. 3 are more common (black spots on a red background) - red morphs, if vice versa - black morphs. He determined that red ones are dominant and black ones are recessive. There are more red ones in winter, black ones in summer. The presence of polymorphism in a population is adaptive in nature.

They study the color of the garden snail in Europe.

In 1960, Hubby and Lewontin proposed the use of electrophoresis to determine the morphs of human and animal proteins. Proteins are distributed into layers due to charge. The method is very accurate. An example is isoenzymes. Organisms of the same species have several forms of enzymes that catalyze one chemical reaction, but differing in structure. Their activity also varies. Their physicochemical properties are also excellent. 16% of structural gene loci are polymorphic. Glucose-6-phosphatase has 30 forms. There is often traction on the floor. The clinic has long distinguished lactate dehydrogenase (LDH), of which there are 5 forms. This enzyme converts glucose into pyruvate; the concentration of one or another isoenzyme in different organs determines what laboratory diagnosis of diseases is based on.

Invertebrate animals are more polymorphic than vertebrates. The more polymorphic a population is, the more evolutionarily plastic it is. In a population, large pools of alleles do not have maximum fitness in a given location at a given time. These reserves occur in small quantities and in a heterozygous state. After changes in living conditions, they can become useful and begin to accumulate - transitional polymorphism. Large genetic reserves help populations respond to their environment. One of the mechanisms that maintain diversity is the superiority of heterozygotes. With complete dominance, there is no manifestation; with incomplete dominance, heterosis is observed. In a population, selection maintains a genetically unstable heterozygous structure, and such a population contains 3 types of individuals (AA, Aa, aa). As a result of natural selection, genetic death occurs, reducing the reproductive potential of the population. The population is falling. Therefore, genetic death is a burden for the population. It is also called genetic load.

Genetic cargo- part of the hereditary variability of a population, which determines the emergence of less fit individuals that are subject to selective death as a result of natural selection.

There are 3 types of genetic load.

Mutational.

Segregation.

Substitutive.

Each type of genetic load correlates with a certain type of natural selection.

Mutation genetic load- side effect of the mutation process. Stabilizing natural selection removes harmful mutations from a population.

Segregation genetic load– characteristic of populations that take advantage of heterozygotes. Less well-adapted homozygous individuals are removed. If both homozygotes are lethal, half of the offspring die.

Substitute genetic load– the old allele is replaced by a new one. Corresponds to the driving form of natural selection and transitional polymorphism.

Genetic polymorphism creates all the conditions for ongoing evolution. When a new factor appears in the environment, the population is able to adapt to new conditions. For example, insect resistance to various types insecticides.

For the first time, the genetic load in the human population was determined in 1956 in the Northern Hemisphere and amounted to 4%. Those. 4% of children were born with a hereditary pathology. Over the following years, more than a million compounds were introduced into the biosphere (more than 6,000 annually). Daily – 63000 chemical compounds. The influence of radioactive radiation sources is growing. The DNA structure is disrupted.

3% of children in the United States suffer from congenital mental retardation (they do not even attend high school).

Currently, the number of congenital abnormalities has increased by 1.5 - 2 times (10%), and medical geneticists say the figure is 12-15%.

Conclusion: protect the environment.

Polymorphism by blood groups.

Everyone acquires blood group antigens higher value in medicine. In some cases, agglutination occurs during blood transfusion - the result of the interaction of the donor's antigen and the recipient's antibodies.

There are 4 blood groups in the ABO system. Each person belongs to only one group.

3 alleles - A, B, O.

JªJª, JªJ° - A

JªJв, Jв J° - В

All human populations are polymorphic in blood groups, but each population will have different frequencies of occurrence. In Sweden the O group is common. Among the Indians, group B is completely absent. Parallel polymorphism in blood groups according to the ABO system has also been found in great apes. Conclusion: polymorphism arose before the emergence of the human species, which means that the human ancestor already had different groups blood.

There is a connection between blood group diseases.

Oh group. Rheumatism is rare, but gastric and duodenal ulcers are more common in populations if they were for a long time in isolation. For example - Aborigines, Indians, indigenous people of Australia. They had natural selection, the reason for which was infectious diseases - cholera, tuberculosis, syphilis.

Alcoholism is an important phenotypic trait. It can be acute or chronic. It appears more often in men. For a long time it was believed that alcoholism develops under environmental conditions; the contribution of heredity was not taken into account. However, it turns out that the genotype is important.

For example, in the case of taking a child from orphanage into the family, the following results were obtained:

True and adoptive parents are alcoholics - 46% of children are alcoholics, and non-alcoholics - 8%.

The true parent is an alcoholic, the adopted parent is not - 50% are alcoholics.

True - not an alcoholic, adopted alcoholic - 14%.

In humans, there are 2 isoenzymes that break down ethyl alcohol - alcohol dehydrogenases. There are ADN1 and ADN2. The faster the breakdown of alcohol, the worse person tolerates alcohol, because As a result of the reaction, an aldehyde is formed, which has toxic properties. ADH1 is less active than ADH2, which is why people with ADH2 cannot tolerate alcohol.

However, there is another enzyme that breaks down the aldehyde, and a person’s tolerance to alcohol also depends on its activity.

Genetic polymorphism is widespread and underlies hereditary predisposition to diseases. However, diseases of hereditary predispositions manifest themselves only through the interaction of genes and environment. Environmental conditions - lack or excess of nutrients, the presence of psychogenic factors, toxic substances, etc. The clinical course of diseases can be varied. The greater the impact of environmental factors, the greater the number of patients with a predisposition to this disease. Diseases are more severe (hypertension, rheumatism, diabetes mellitus and others),

There are monogenic and polygenic diseases.

Monogenic diseases of hereditary predisposition are hereditary diseases that appear due to a mutation of one gene or appear under the influence of a certain environmental factor (autosomal recessive or X-linked).

Manifest when exposed to factors:

Physical;

Chemical;

Food;

Environmental pollution.

Paramyotomy - in damp weather, tonic muscle spasms occur in the cold, under the influence of heat - they disappear. The disease is associated with a heat-sensitive protein. The reaction manifests itself in infancy and does not change throughout a person’s life.

Xeroderma pigmentosum is a special type of freckled skin. Appears at 4-6 years of age. Children cannot tolerate UV light; malignant tumors arise; such children die from metastases before the age of 15. They also cannot tolerate gamma rays.

Bloom's syndrome. Pigmented “butterfly” on the face, small stature, elongated head. Jews, Poles, Belarusians, Austrians. Die before the age of 18. They do not tolerate UV irradiation or gamma rays.

Alpha-1 antitrypsin in air pollution and tobacco smoke is manifested by acute blockage of the bronchi or cirrhosis of the liver.

Among Caucasians, milk intolerant people account for 10-20%, in Africa - 70-80%.

Effect of drugs: sulfonamide drugs provoke blood diseases.

There are polygenic diseases of hereditary origin - diseases that arise under the influence of many factors (multifactorial) and as a result of the interaction of many genes. It is very difficult to establish a diagnosis in this case, because Many factors operate, and a new quality appears when factors interact.

Wide polymorphism helps the population adapt to environmental conditions. In healthy people there is no contradiction between the environment and the genotype; if this contradiction arises, diseases of hereditary predisposition appear. Any classification of diseases includes a group of similar diseases.

Genetic polymorphism is a condition in which there is long-term diversity of genes, but the frequency of the rarest gene in the population is more than one percent. Its maintenance occurs due to constant mutation of genes, as well as their constant recombination. According to research conducted by scientists, genetic polymorphism has become widespread, because there can be several million gene combinations.

Large stock

Better adaptation of a population to a new environment depends on a large supply of polymorphism, and in this case evolution occurs much faster. It is not practical to estimate the entire number of polymorphic alleles using traditional genetic methods. This is due to the fact that the presence of a certain gene in the genotype is achieved by crossing individuals that have different phenotypic characteristics determined by the gene. If you know what part of a certain population consists of individuals with different phenotypes, then it becomes possible to determine the number of alleles on which the formation of a particular trait depends.

How it all began?

Genetics began to develop rapidly in the 60s of the last century, it was then that enzymes in gels began to be used, which made it possible to determine genetic polymorphism. What is this method? It is with its help that proteins move in an electric field, which depends on the size of the protein being moved, its configuration, as well as the total charge in different parts of the gel. After this, depending on the location and number of spots that appear, the identified substance is identified. To assess protein polymorphism in a population, it is worth examining approximately 20 or large quantity loci. Then, using a mathematical method, the number and ratio of homo- and heterozygotes are determined. According to research, some genes can be monomorphic, while others can be unusually polymorphic.

Types of polymorphism

The concept of polymorphism is extremely broad; it includes a transitional and a balanced variant. This depends on the selective value of the gene and natural selection, which puts pressure on the population. In addition, it can be genetic and chromosomal.

Gene and chromosomal polymorphism

Gene polymorphism is represented in the body by more than one allele; a striking example of this is blood. Chromosomal represents differences within chromosomes that occur due to aberrations. However, there are differences in heterochromatic regions. In the absence of pathology that will lead to impairment or death, such mutations are neutral.

Transitional polymorphism

Transitional polymorphism occurs when an allele that was once common is replaced in a population by another that provides its carrier with greater adaptability (also called multiple allelism). With a given variety, there is a directional shift in the percentage of genotypes, due to which evolution occurs and its dynamics are carried out. The phenomenon of the industrial mechanism may become good example, which characterizes transitional polymorphism. What it is is shown by a simple butterfly, which, with the development of industry, replaced White color their wings on the dark. This phenomenon began to be observed in England, where more than 80 species of butterflies turned from pale cream flowers to dark ones, which was first noticed after 1848 in Manchester due to the rapid development of industry. Already in 1895, more than 95% of moths acquired a dark coloration of their wings. Such changes are associated with the fact that tree trunks have become more smoky, and light-colored butterflies have become easy prey for thrushes and robins. The changes occurred due to mutant melanistic alleles.

Balanced polymorphism

The definition of “balanced polymorphism” characterizes the absence of a shift in any numerical ratios various forms genotypes in a population that is in stable environmental conditions. This means that from generation to generation the ratio remains the same, but may fluctuate slightly within a certain value, which is constant. In comparison with transitional, balanced polymorphism - what is it? It is primarily a static evolutionary process. I. I. Shmalhausen in 1940 also gave it the name equilibrium heteromorphism.

Example of balanced polymorphism

A clear example of balanced polymorphism is the presence of two sexes in many monogamous animals. This is due to the fact that they have equal selective advantages. Their ratio within one population is always equal. If there is polygamy in a population, the selective ratio of representatives of both sexes may be disrupted, in which case representatives of one sex can either be completely destroyed or are eliminated from reproduction in to a greater extent than representatives of the opposite sex.

Another example would be the blood group according to the ABO system. In this case, the frequency of different genotypes in different populations may be different, but at the same time it does not change its constancy from generation to generation. Simply put, no one genotype has a selective advantage over another. According to statistics, men with the first blood group have a longer life expectancy than other members of the stronger sex with other blood groups. Along with this, the risk of developing duodenal ulcer in the presence of the first group is higher, but it can perforate, and this will cause death if assistance is delayed.

Genetic balance

This fragile state can be disrupted in a population as a consequence of the occurrence, and they must occur with a certain frequency and in each generation. Studies have shown that polymorphisms of genes of the hemostatic system, the decoding of which makes it clear whether the evolutionary process promotes these changes or, conversely, counteracts them, are extremely important. If you trace the course of the mutant process in a particular population, you can also judge its value for adaptation. It can be equal to one if the mutation is not excluded during the selection process and there are no obstacles to its spread.

Most cases show that the value of such genes is less than one, and in the case of the inability of such mutants to reproduce, everything comes down to 0. Mutations of this kind are swept aside in the process of natural selection, but this does not exclude repeated changes in the same gene, which compensates for elimination which is carried out by selection. Then equilibrium is reached, mutated genes can appear or, conversely, disappear. This leads to a balanced process.

An example that can clearly characterize what is happening is sickle cell anemia. In this case, a dominant mutated gene in a homozygous state contributes to the early death of the organism. Heterozygous organisms survive but are more susceptible to malaria disease. Balanced polymorphism of the sickle cell anemia gene can be traced in areas where this tropical disease is widespread. In such a population, homozygotes (individuals with the same genes) are eliminated, and selection acts in favor of heterozygotes (individuals with different genes). Due to the multi-vector selection occurring in the gene pool of the population, genotypes are maintained in each generation, which ensure better adaptability of the organism to environmental conditions. Along with the presence of the sickle cell anemia gene, there are other types of genes that characterize polymorphism. What does this give? The answer to this question will be a phenomenon called heterosis.

Heterozygous mutations and polymorphism

Heterozygous polymorphism provides for the absence of phenotypic changes in the presence of recessive mutations, even if they are harmful. But at the same time, they can accumulate in the population up to high level, which may exceed harmful dominant mutations.

evolutionary process

The evolutionary process is continuous, and its prerequisite is polymorphism. What this means is the constant adaptability of a particular population to its habitat. Organisms of different sexes that live within the same group can be in a heterozygous state and transmitted from generation to generation for many years. Along with this, their phenotypic manifestation may not exist - due to the huge reserve of genetic variability.

Fibrinogen gene

In most cases, researchers consider fibrinogen gene polymorphism as a precursor to the development of ischemic stroke. But in this moment The problem in which genetic and acquired factors are able to influence the development of this disease comes to the fore. This type of stroke develops due to thrombosis of the cerebral arteries, and by studying the polymorphism of the fibrinogen gene, one can understand many processes, by influencing which the disease can be prevented. At present, scientists have not sufficiently studied the connections between genetic changes and biochemical blood parameters. Further research will make it possible to influence the course of the disease, change its course, or simply prevent it in the future. early stage development.

) two or more different hereditary forms that are in dynamic equilibrium over several or even many generations. Most often, genetic selection is determined either by varying pressures and vectors (direction) of selection in different conditions(for example, in different seasons), or increased relative viability of heterozygotes (See Heterozygote). One of the types of genetic diversity—balanced genetic diversity—is characterized by a constant optimal ratio of polymorphic forms, deviation from which turns out to be unfavorable for the species and is automatically regulated (the optimal ratio of forms is established). The majority of genes are in a state of balanced gene production in humans and animals. There are several forms of genetic diversity, the analysis of which makes it possible to determine the effect of selection in natural populations.

Lit.: Timofeev-Resovsky N.V., Svirezhev Yu.M., On genetic polymorphism in populations, “Genetics”, 1967, No. 10.

Great Soviet Encyclopedia. - M.: Soviet Encyclopedia. 1969-1978 .

See what “Genetic polymorphism” is in other dictionaries:

genetic polymorphism- Long-term existence in a population of two or more genotypes, the frequencies of which reliably exceed the probability of occurrence of corresponding repeated mutations. [Arefyev V.A., Lisovenko L.A. English-Russian explanatory dictionary of genetic terms... ... Technical Translator's Guide

Genetic polymorphism genetic polymorphism. The long-term existence in a population of two or more genotypes, the frequencies of which significantly exceed the probability of occurrence of the corresponding repeated mutations. (Source: “Anglo-Russian intelligent... ...

genetic polymorphism- genetinis polimorfizmas statusas T sritis ekologija ir aplinkotyra apibrėžtis Genetiškai skirtingų dviejų ar daugiau vienos rūšies formų egzistavimas populiacijoje, kurio negalima laikyti pasikartojančiomis mutacijomis. atitikmenys: engl. genetic... Ekologijos terminų aiškinamasis žodynas

genetic polymorphism- genetinis polimorfizmas statusas T sritis augalininkystė apibrėžtis Ilgalaikis buvimas populiacijoje dviejų ar daugiau genotipų, kurių dažnumas labai viršija pasikartojančių mutacijų radimosi tikimybę. atitikmenys: engl. genetic polymorphism rus... Žemės ūkio augalų selekcijos ir sėklininkystės terminų žodynas

Genetic polymorphism- long-term existence in a population of two or more genotypes, the frequencies of which reliably exceed the probability of occurrence of corresponding repeated mutations... Dictionary of psychogenetics

Polymorphism in biology, the presence within one species of individuals that are sharply different in appearance and do not have transitional forms. If there are two such forms, the phenomenon is called dimorphism ( special case- sexual dimorphism). P. includes differences in appearance... ...

I Polymorphism (from the Greek polýmorphos diverse) in physics, mineralogy, chemistry, the ability of some substances to exist in states with different atomic crystal structures. Each of these states (thermodynamic phases),... ... Great Soviet Encyclopedia

Polymorphism of a unique event, English. unique event polymorphism/UEP in DNA genealogy means a genetic marker corresponding to one extremely rare mutation. It is believed that all carriers of such a mutation inherit it from... ... Wikipedia

Discontinuous variation in homologous alleles of the same gene locus, on which the stability of a population is based. Sensitivity of organisms to various factors environment differentiated, genotypically determined,... ... Ecological dictionary

Polymorphism polymorphism. The existence of genetically different individuals in a crossing group (population); P. may have a non-genetic (modifying) nature, for example, depending on population density (see. ) … Molecular biology and genetics. Dictionary.

Combination Greek words poly (meaning several) and morph (meaning shape), polymorphism is a term used in genetics to describe multiple forms of a single gene that exists in an individual or among a group of individuals. What is genetic polymorphism? Where monomorphism means having only one form and dimorphism only two forms exist, the term polymorphism is a very specific term in genetics and biology referring to the multiple forms of a gene that

Combination of Greek words poly(which means several) and morph(meaning form), polymorphism is a term used in genetics to describe multiple forms of a single gene that exist in an individual or among a group of individuals.

What is genetic polymorphism?

Where monomorphism means having only one form and dimorphism only two forms exist, the term polymorphism is a very specific term in genetics and biology referring to the multiple forms of a gene that can exist.

The term does not apply to character traits with continuous change, such as height (even though this may be an inherited aspect). Instead, polymorphism refers to forms that are discontinuous (having discrete variation), bimodal (having or involving two modes), or polymodal (multiple modes). For example, the ear tips are either attached or they are not, it is an either/or situation, and not like the height, which is not a set number.

Polymorphism was originally used to describe the visible forms of genes, but the term is now used to include critical modes such as blood types that require a blood test to decipher. Additionally, the term is sometimes used incorrectly to describe apparently different geographic races or variants, but polymorphism refers to the fact that multiple forms of a single gene must simultaneously occupy the same habitat (which excludes geographic, racial, or seasonal morphs.)

Genetic polymorphism refers to the occurrence of two or more genetically defined phenotypes in a given population (in proportions such that the rarest characteristics cannot be maintained by repeated mutation alone). Polymorphism promotes diversity and persists over many generations because no one form has an overall advantage or disadvantage over others from the point of view of natural selection.

Is this the same as a mutation?

Mutations themselves are not classified as polymorphisms. Polymorphism is a variation in DNA sequence that is common to a population. On the other hand, a mutation is any change in DNA sequence away from the norm (implying that a normal allele runs through a population and that the mutation changes that normal allele to a rare and abnormal variant.)

In a polymorphism, there are two or more equally acceptable alternatives and classified as a polymorphism, the smallest common allele must have a frequency of 1% or more in the population. If the frequency is below this, the allele is considered a mutation.

Polymorphism and enzymes

Gene sequencing studies, such as those done for the Human Genome Project, have shown that at the nucleotide level, the gene encoding a specific protein can have a number of differences in sequence. These differences do not change the overall product significant enough to produce a different protein, but may have a substrate effect. specificity and specific activity (for enzymes), binding efficiency (for transcription factors, membrane proteins, etc.) or other functions and functions. For example, there are many different polymorphisms of CYP 1A1, one of the many liver cytochrome P450 enzymes, in the human race.

Although the enzymes essentially share the same sequence and structure, polymorphisms in the enzyme can influence how people metabolize drugs. Polymorphisms of CYP 1A1 in humans, where the amino acid Isoleucine is replaced by Valine in exon 7, have been associated with smoking-related smoking.

The use of genetic polymorphisms has been one of the strengths deCODE Genetics, a company that focuses on identifying genetic risk factors for various diseases.

Sources:

Ford, E. B. 1975. Environmental genetics(4th ed.). London: Chapman & Hall

Ford, E. B. (1940). "Polymorphism and Taxonomy". In Julian Huxley (ed.). New taxonomy. Oxford: Clarendon Pr. pp. 493-513. ISBN 1-930723-72-5.

Sheppard, Philip M. 1975. Natural selection and inheritance(4th ed.) London: Hutchinson.

LECTURE No. 17

In medical biology and genetics

For 1st year students

Curative, medical-preventive and medical-diagnostic

Faculties

Topic: “POPULATION - SPECIES LEVEL

ORGANIZATIONS OF LIVING.

GENETIC POLYMORPHISM OF THE HUMAN POPULATION".

Time - 90 min.

Educational and educational goals:

1. Know the ecological and genetic characteristics of populations.

2. Familiarize yourself with the features of the population structure of humanity.

3. Point out the influence of elementary evolutionary factors on the human population.

4. Familiarize yourself with the frequency of hereditary diseases in human populations.

LITERATURE:

1. Bekish O.-Ya. L. Medical biology. Course of lectures for medical students. Universities. - Vitebsk, 2000 p. 296-309.

2. Biology /Ed. V.N. Yarygina / 1st book - M.: Vsh, 1997. With. 32-49.

3. O.-Ya. L. Bekish, L.A. Khramtsova. Medical workshop biology. - Ed. "White Wind", 2000 - p. 135-141.

MATERIAL SUPPORT

1. Multimedia presentation.

CALCULATION OF STUDY TIME

Slide 3

Species of living organisms are represented by populations. Population – a sufficiently numerous collection of individuals of the same species inhabiting a certain territory for a long time, within which free interbreeding takes place and which is isolated from neighboring populations of individuals.

A population represents the ecological, morphophysiological and genetic unity of individuals of a species. In the evolutionary process it is an indivisible unit, i.e. is an independent evolutionary structure. A population is an elementary evolutionary unit.

It is not individuals that evolve, but groups of individuals—populations. This is the smallest of the groups, capable of independent evolution. Populations are characterized by environmental and genetic characteristics.

Slide 4

Environmental characteristics - size of the occupied territory, density, number of individuals, age and sex structure, population dynamics.

Slide 5

Genetic characteristics - population gene pool (complete set of population genes). The gene pool is described in terms of the frequency of occurrence of allelic variants of genes or concentration.

Slide 6

The gene pool of the population is characterized by:

1) Unity . The unity of the gene pool of a population lies in the desire of the species, as closed system, maintain their homogeneity in hereditary properties.

2) Genetic polymorphism. Natural populations are heterogeneous, they are saturated with mutations. When there is no pressure external factors this heterogeneity is in a certain equilibrium.

3) Dynamic balance of genes .

Slide 7

The population includes individuals with both dominant and recessive traits that are not under the control of natural selection. However, the dominant allele does not replace the recessive one. The discovered pattern is called Hardy-Weinberg law for an ideal population. This is a population with a large number, free crossing (panmixia), lack of mutations, migrations and natural selection.

In an ideal population, the ratio of genotypes of dominant homozygotes AA, heterozygote Ahh and recessive homozygotes ahh remain constant:

Slide 8

If the gene frequency A equal to R , and the gene frequency A equal to q , then their concentration Ap + aq = 1.

The combination of gametes gives the distribution of genotypes according to the formula:

Hardy-Weinberg law formula:

(Ap + aq)(Ap + aq) = AA p 2 + 2Aa pq + aaq 2 = (Ap + aq) 2 = 1

Quantities p 2, 2pq and q 2 - remain constant, this explains the fact that individuals with recessive traits are preserved along with dominant ones. The ratio of homo- and heterozygotes does not change with different options reciprocal crosses:

Hardy-Weinberg Law:

“In a large panmix population, where there is no selection, mutation, or migration, a constant distribution of homo- and heterozygotes is observed. Knowing the frequency of the recessive gene, we can use a formula to determine the frequency of the dominant allele and vice versa.”

Slide 9

In human genetics, a population is a group of people occupying a certain territory and intermarrying freely. They are large and small in number. Large human populations consist not of one, but of several anthropological groups, differing in origin and scattered over large areas. Such populations include more than 4 thousand people. The human population is not panmix, but represents a huge collection of numerous closed groups.

Slide 10

Evolutionary factors acting on human populations lead to changes in the gene pool. The influence of elementary evolutionary factors on changes in the gene pool of human populations comes down to action mutation process, migrations, genetic drift, natural selection.

Slide 11

Mutation process is a constantly operating elementary evolutionary factor. It provides population variability for individual genes. Mutations are the elementary material of evolution. The frequency of occurrence of individual spontaneous mutations is in the range of 10 -4 - 10 -8. The pressure of the mutation process is determined by the change in the frequency of an allele in relation to another. The mutation process constantly maintains the heterogeneity of the population, but the prevalence of heterozygotes Ahh over homozygotes ahh significant, since most pathological mutations are recessive. Considering a large number of genes in humans, it should be assumed that up to 10% of its gametes carry mutant genes. Dominant mutations appear already in the first generation and are immediately subject to the action of natural selection. Recessive - accumulate, appear phenotypically only in the homozygous state. The accumulation of mutant alleles creates population heterogeneity and contributes to combinative variability. The average degree of heterozygosity in humans is 6.7%, and in vertebrates as a whole it is 6.0%. Considering that a person has about 32,000 structural genes, this means that each person is heterozygous for more than 2,000 loci. At the same time, the theoretically possible number various types gametes are 2 2150. Such a number of gametes cannot be formed not only in an individual person, but also in all of humanity over the entire period of its existence. This value is significant more number protons and neutrons in the Universe.

The saturation of a population with recessive genes reduces the fitness of individuals and is called genetic load. The presence of genetic load in human populations is explained by the appearance of 5% of descendants with genetic defects.

Slide 12

Genetic drift - These are fluctuations in gene frequencies over a number of generations caused by random reasons, for example, small populations. Genetic drift is a completely random process and belongs to a special class of phenomena called sampling errors. General rule is that the value sampling errors is in inverse relationship from sample size. In relation to living organisms, this means that the smaller the number of interbreeding individuals in a population, the more changes in allele frequencies will undergo due to genetic drift.

A random increase in the frequency of one mutation is usually caused by preferential reproduction in isolated populations. This phenomenon is called "ancestor effect" . It occurs when several families create a new population in a new territory. It supports high degree marital isolation, which contributes to the fixation of some alleles and the elimination of others. The consequences of the “effect” are the uneven distribution of hereditary diseases in human populations on earth.

Random changes in allele frequencies, similar to those caused by the “ancestor effect,” also occur if a sharp reduction in population occurs in the process of evolution.

Genetic drift leads to:

1) changes in the genetic structure of populations: increased homozygosity of the gene pool;

2) reducing the genetic variability of populations;

3) divergence of populations.

Slide 13

Insulation - This is a restriction on freedom of interbreeding. It promotes divergence - the division of populations into separate groups and changes in the frequencies of genotypes. In human populations, ecological and ethological isolation is more significant. It includes religious, moral and ethical restrictions on marriage, class, clan, property, professional and others. Isolation of populations leads to consanguineous marriages - inbreeding and genetic drift. Consanguineous marriages are:

1) incest (forbidden) - between first degree relatives;

2) consanguineous - between second and third degree relatives.

They lead to the manifestation of recessive pathological genes in a homozygous state, which contributes to mortality.

Slide 14

The effect of consanguineous marriages in Japan according to W. J. Schull and J. V. Neel

Slide 15

Migration or gene flow - This is the movement of individuals from one population to another and the crossing of immigrants with representatives of the local population. Gene flow does not change allele frequencies in the species as a whole, but in local populations they can change if the initial allele frequencies in them are different. Even minor migration, such as one individual per thousand per generation, is sufficient to prevent differentiation of moderately sized populations.

Slide 16

Natural selection performs the function of stabilizing the gene pool in human populations, as well as maintaining hereditary diversity. The main purpose of the action of natural selection is the preservation of individuals with beneficial traits and death with harmful traits, as well as differential reproduction (the contribution of an individual to the gene pool of a population during selective reproduction).

The frequency of some genes in the human population changes under the influence of selection. The action of selection in human populations is confirmed by the facts of spontaneous abortions and perinatal mortality in humans. So more than 42% of spontaneous abortions occur due to the lethal effect of chromosomal abnormalities. Chromosomal abnormalities cause spontaneous abortions, which reach 70% during the first trimester of pregnancy, 30% in the second, and 4% in the third. Perinatal mortality in 6.2% of cases is caused by chromosomal pathology. Among stillbirths, 6% have lethal chromosomal abnormalities.

The action of selection ensures the ability of an organism to contribute to the genetic composition of the future generation. This is done in two ways:

1) selection for survival;

2) the use of genetic factors influencing reproduction.

Changes in the gene pools of populations always occur under the influence of a complex set of evolutionary factors. The relationship between selection and mutation pressure is important. If a given allele is supported by selection, then carriers of this allele, being more fit, are characterized by preferential reproduction. As a result, selection crowds out all other alleles. Natural selection in human populations acts both against homozygotes (dominant and recessive) and heterozygotes.

Slide 17

Slide 18

The influence of elementary evolutionary factors on the genetic diversity of populations.

Slide 19

Genetic polymorphism of human populations.

Polymorphism (multiformity) is any variety of forms of the same type of organism. Polymorphism is the most universal phenomenon of life. J.B.S. Haldane called humans the most polymorphic species on Earth. In humans, almost all characteristics are polymorphic (eye color, hair color, shape of the nose and skull, blood type, etc.). Polymorphism can be the result of either discrete intrapopulation variability of a hereditary nature, or it can be determined by the reaction norm.

Slide 20

Genetic polymorphism occurs due to the fixation of different mutations in the population. Therefore it is classified into: genetic, chromosomal and genomic.

Slide 21

Gene polymorphism caused by the presence of two or more alleles. For example, the ability of humans to taste phenylthiourea is determined by the dominant allele ( TT, Tt), recessive homozygotes ( tt) – they don’t feel it. Inheritance of blood groups is determined by three alleles - A, B, O. Chromosomal polymorphism is associated with chromosomal aberrations, and genomic polymorphism is associated with changes in sets of chromosomes in the karyotype (heteroploidy).

Slide 22

Polymorphic genetic systems, by their presumed nature, include three groups of polymorphisms: transitory, neutral, balanced.

Slide 23

Transient polymorphism is explained by a change in the genetic composition of the population at the locus in question. One new allele under changed environmental conditions becomes more advantageous and replaces the “original” one. Such polymorphism cannot be stable because, due to natural selection, sooner or later the “original” allele will be replaced by a new one and the population will be monomorphic for the “new” allele. The speed of such a process cannot be noticed over the life of one generation.

Slide 24

At neutral polymorphism due to random stochastic processes (genetic drift, founder effect), random changes in allele frequencies occur. For example, the emergence of differences in adaptive-indifferent characteristics (attached or free earlobe). Changes in gene frequencies for these traits are carried out by the mechanism of genetic drift, which explains the neutral type of their evolution.

Slide 25

Balanced polymorphism - it is a polymorphism caused by a complex balance between selection against both homozygotes in favor of the heterozygote. The recessive genotype undergoes stronger elimination than the dominant one. Differences in the rate of elimination of these two genotypes support a constant, stable equilibrium existence in the population of both alleles with their own frequency. This explains the stability of such polymorphism. The most fully studied systems of balanced polymorphism associated with selection for malaria are abnormal hemoglobins, thalassemia, and deficiency of the erythrocyte enzyme glucose-6-phosphate dehydrogenase. The stability of these polymorphisms disappears due to successes in the fight against malaria. Balanced polymorphism turns into transient. However, to reduce gene frequencies of now completely pathological genes, since there is no need for protection against malaria, several tens of generations must pass.

The large number of polymorphic systems discovered to date in humans with a significant number of alleles leads to the fact that almost every person has a unique set of genes, which allows us to talk about the biochemical and immunological individuality of the individual. It has great importance in medical practice, especially in forensic science.

Typically, hereditary predisposition is multifactorial in nature and is determined by many genes, with a predominant effect of one or more genes. To identify these genes, biochemical and immunological methods of anthropogenetics are used. Currently, more than 130 polymorphic gene loci encoding polymorphic proteins have been described. These are enzyme proteins, antigens, transport proteins, etc. It is argued that about one third of a person's structural genes should have multiple alleles, i.e. encode polymorphic metabolic products. In such a large choice for genetic recombination lies the possibility of the emergence of individuals with unfavorable combinations of genes that determine hereditary predisposition to diseases. Taking into account genetic polymorphism, to specifically determine the genetic factor of predisposition to a disease, the frequency of occurrence of certain polymorphic proteins (antigens) in a given disease and in a control group of healthy people is compared. There is numerous information on associations of diseases with immunological markers - blood group antigens ABO, HLA system, with blood haptoglobins and with the secretor. In particular, the predisposition of people with group 2 ( A) blood to cancer of the stomach, colon, ovary, cervix, rheumatism, coronary heart disease, thromboembolism, etc. People with blood group 1 ( ABOUT) are predisposed to diseases of gastric and duodenal ulcers, etc.