Gene penetrance reflects. Penetrance and expressivity, the phenotypic manifestation of a gene can. Pleiotropic action of genes

Drug- a chemical agent that causes stupor, coma, or insensitivity to pain.

The effect of drugs on the offspring of a drug addict is detrimental. This is due to mutagenic effect of narcotic substances on sperm and eggs, with both a direct toxic effect on the development of the embryo. If the expectant mother does not stop taking drugs during pregnancy, then the child may be born addicted to drugs. If this does not happen, then The risk of drug addiction continues throughout your life.

Direct effect of drugs on the fetus begins from the very first seconds of conception. Drugs can directly affect the fetus, destroying his cellular structure, or through change shell uterus, impair blood supply to the fetus and cause periodic hypoxia. Liver the developing organism is also located on stages formation, That's why drugs, penetrating To fetus can linger And unhindered destroy gradually systems And organs unborn organismism.

It is natural that risk of stillbirth among drug addicts is incredibly high - 80%, placental abruption – 15%, premature birth,

Children have an increased risk of congenital malformations, growth retardation or postnatal psychobehavioral disorders (which manifests themselves in hyperactivity, hypertonicity and poor learning, mental retardation, even severe dementia is possible), skeletal abnormalities and isolated atresias occur in newborns.

A child born to a mother who is a drug addict shows signs of drug addiction from the first hours of life. His body requires the drugs that he received in the blood from his mother, the body reacts to this with convulsions, crying and other manifestations characteristic of adult drug addicts in a state of withdrawal.

I(0) "hunter"	II(A) "farmer"			III(B) "nomad"		IV(AB) "riddle »
Origin
The oldest and most widespread appeared 40,000 years ago. The ancestors led the lifestyle of hunters and gatherers. The immune system is strong and resilient. It is believed that Neanderthals and Cro-Magnons, from whom man descended, had this blood type.	Generated by the first population migrations, it appeared when the need arose to switch to food from agricultural products and accordingly change the way of life - between 25,000 and 15,000 BC. Everyone was required to be able to cooperate with others within the community.			People with the third blood group appeared as a result of the merging of populations and adaptation to new climatic conditions 10-15 thousand years ago in the foothills of the Himalayas. It represents nature's desire to strike a balance between enhanced mental activity and the demands of the immune system.		It appeared unexpectedly about a thousand years ago, not as a result of adaptation to changing living conditions, like other blood groups, but as a result of the mixing of Indo-Europeans and Mongoloids.
Diseases	Blood type 0 (I)	Blood type A (II).	Blood type B (III)		Blood type AB (IV).
Diseases of the gastrointestinal tract	predisposition to peptic ulcer of the stomach and duodenum.	predisposition to gastritis with low acidity, formation of stones in the bile ducts, chronic cholecystitis.	tendency to colon tumors, pancreatic diseases.		Resistance to peptic ulcers. Women's tendency to pancreatic diseases.
Dental diseases	Resistance to caries	Predisposition to caries	Predisposition to caries, but the course of the disease is more favorable.		Resistance to caries
Diseases of the cardiovascular system	High risk of developing hypertension. High cholesterol, atherosclerosis, obesity. Increased blood clotting: thrombosis, thrombophlebitis,	Heart disease, coronary disease, tendency to rheumatism and myocardial infarction	resistance to myocardial infarction		Heart diseases. High cholesterol, atherosclerosis, obesity. Increased blood clotting: thrombosis, thrombophlebitis.
	Colon tumors are rare and the prognosis of the disease is often favorable	Predisposition to the development of stomach cancer, leukemia, blood cancer.	Predisposition to colon cancer. In women, pancreatic cancer, ovarian cancer		In women, pancreatic cancer, ovarian cancer
Diseases of the blood system	Hemophilia is common	Acute leukemia
Thyroid diseases		Predisposition to thyroid diseases
Nervous system diseases	Patients with schizophrenia are less common		neuroses and psychoses
Diseases of the kidneys and genitourinary system	Kidney stones, group at highest risk of developing the disease	Kidney stone disease	Frequent urinary tract infections. Women in group 3 are prone to diseases of the ovaries and pancreas.		Resistant group to these diseases Women in group 4 are prone to ovarian diseases
Skin diseases					Rarely found
Infectious diseases	People often get sick with influenza A.
Lung diseases	Very susceptible to developing diseases of the bronchi and lungs

When considering the action of a gene and its alleles, it is necessary to take into account not only gene interactions and the action of modifier genes, but also the modifying effect of the environment in which the organism develops. It is known that the primrose flower color is pink (P-) - white (pp) is inherited according to a monohybrid pattern if plants develop in the temperature range of 15-25°C. If the plants F 2 grown at a temperature of 30-35°C, then all their flowers turn out to be white. Finally, when growing plants F 2 under conditions of temperature fluctuating around 30°C, it is possible to obtain various ratios from 3Р:1рр up to 100% of plants with white flowers. Such a varying ratio of classes during splitting depending on environmental conditions or on the conditions of the genotypic environment (as S.S. Chetverikov called the variation of the genotype by modifier genes) is called varying penetrance: This concept implies the possibility of manifestation or non-display of a trait in organisms that are identical in terms of the genotypic factors under study.

An example of the pleiotropic effect of a gene has already been mentioned - the dominant platinum coloration of foxes with a recessive lethal effect. As shown by D.K. Belyaev and his colleagues, it is possible to achieve the birth of live puppies, homozygous for the dominant allele of platinum coloring, if the length of the day for pregnant females is varied. Thus, the penetrance of the lethal effect can be reduced (it will no longer be 100%).

Penetrance is expressed by the proportion of individuals exhibiting the studied trait among all individuals of the same genotype for the controlled (studied) gene.

The degree of expression of the trait may also depend on the external environment and modifier genes. For example, Drosophila, homozygous for the allele vgvg(rudimentary wings), displays this feature more contrastingly as the temperature decreases. Another sign of Drosophila is the absence of eyes. (eyey) varies from 0 to 50% of the number of facets characteristic of wild-type flies.

The degree of manifestation of a varying trait is called expressiveness. Expressivity is usually expressed quantitatively depending on the deviation of the trait from the wild type.

Both concepts - penetrance and expressiveness - were introduced in 1925 by N.V. Timofeev-Resovsky to describe the varying expression of genes (Fig. 1).

Rice. 1 - Scheme explaining the variation in the expressivity and penetrance of a trait

The fact that a trait may or may not appear in individuals of a given genotype depending on conditions or vary in different environmental conditions convinces us that the phenotype is the result of the action (and interaction) of genes in the specific conditions of the organism’s existence.

The ability of a genotype to manifest itself in one way or another under different environmental conditions reflects the norm of its reaction - the ability to respond to varying development conditions. The reaction rate of the genotype must be taken into account both during experiments and when breeding new forms of economically valuable organisms. The absence of changes in the manifestation of the trait indicates that the influence used does not affect this reaction norm, and the death of the organism indicates that it is already outside the reaction norm. The selection of highly productive forms of plants, animals and microorganisms largely represents the selection of organisms with a narrow and specialized reaction rate to external influences such as fertilizers, abundant feeding, cultivation patterns, etc.

An artificial narrowing or shift in the reaction norm is used to mark many vital genes. Thus, genes that control DNA reproduction and protein synthesis in bacteria and yeast, genes that control the development of Drosophila, etc. were studied. In this case, mutants were obtained that were not viable at elevated cultivation temperatures, i.e. conditionally lethal.

Thus, the material discussed in this chapter shows that the genotype is a system of interacting genes that manifest themselves phenotypically depending on the conditions of the genotypic environment and living conditions. Only through the use of the principles of Mendeleevian analysis can we conditionally decompose this complex system into elementary characteristics - phenes and thereby identify individual, discrete units of the genotype - genes.



When considering the effect of a gene and its alleles, they take into account not only gene interactions, but also the effect of modifier genes and the modifying effect of the environment in which the organism develops.

Primrose flowers are pink (R_) and white (pp) is inherited according to a monohybrid pattern if the plant develops in the interval t- 15-25 °C. If the plant F 2 grow at / = 30-35 °C, then all its flowers will be white. When growing plants F 2 under conditions of temperature fluctuating around 30 °C, it is possible to obtain various ratios from 3 R_ : 1 pp up to 100% of plants with white flowers. This relationship of genes depends on environmental conditions and the conditions of the genotypic environment. S.S. It's called Chetverikov varying penetrance. This concept implies the possibility of manifestation or non-manifestation of traits in organisms that are identical in terms of the genotypic factors under study. Belyaev achieved the birth of live fox puppies (see Fig. 2.5), homozygous for the dominant allele, platinum coloring, by varying the day length for pregnant females. In this regard, the penetrance of the lethal effect can be eliminated.

Penetrance is expressed by the proportion of individuals exhibiting the trait under study among all individuals of the same genotype for the gene being studied.

The degree of expression of the trait may depend on the external environment and modifier genes. Drosophila homozygous for the wing rudimentary allele exhibits this trait more contrastingly when the ambient temperature decreases. Another feature of Drosophila - the absence of eyes - varies from 0 to 50% depending on the number of facets characteristic of a given type of fly.

The degree of manifestation of a varying trait is called expressiveness. Expressivity is expressed quantitatively, depending on the deviation of the trait from the wild type.

Concepts penetrance And expressiveness introduced into genetics in 1925 by Timofeev-Resovsky to describe the varying expression of genes. The fact that a trait is manifested or not manifested in individuals of a given genotype, depending on the conditions, indicates that this is the result of the interaction of genes in the specific conditions of the organism’s existence. The ability of a genotype to manifest itself in one way or another under different environmental conditions reflects the norm of its reaction - the ability to respond to varying development conditions. This fact is taken into account during experiments and when introducing new forms of economically valuable organisms. The absence of changes indicates that the effect used does not affect this reaction norm, and the death of the organism indicates that it is outside the reaction norm.

Selection of plants, animals, microorganisms is the selection of organisms with a narrow and specialized norm of reaction to external influences: fertilizer, abundant feeding, nature (and technology) of cultivation.

An artificial narrowing or shift in the reaction norm is used to mark vital genes. This method was used to study genes that control DNA reproduction, protein synthesis in bacteria and yeast, and genes that control the development of Drosophila. In all cases, mutants were obtained that were not viable at elevated cultivation temperatures, i.e., conditionally lethal.

A genotype is a system of interacting genes that manifest themselves phenotypically depending on the conditions of the genotypic environment and living conditions. Thanks to the principles of Mendelian analysis, it is possible to conditionally decompose any complex system into elementary traits-phenes and thereby identify individual discrete units of the genotype - genes.

Test questions and assignments:

• 1. Give the concept of the terms dominance and recessivity.
• 2. What is a monohybrid cross?
• 3. How does splitting by characteristics occur? Name the genes that carry heredity.
• 4. Explain how independent combination (dihybrid crossing) occurs.
• 5. Explain the splitting of characters in a trihybrid cross. Talk about multiple alleles.
• 6. Name the types of gene interactions.
• 7. Explain the phenomena of penetrance and expressivity.
• 8. What is complementary gene interaction?
• 9. What types of gene interactions that lead to deviations from Mendelian patterns do you know?
• 10. What is the difference between dominance and epistasis?
• 11. Do external conditions affect the manifestation of the action of a gene?
• 12. Give examples of polymeric and pleiotropic action of a gene.

M

Nikolai Vladimirovich Timofeev-Resovsky

intergenic interactions, interallelic interactions, the complexity and ramification of metabolic processes in which proteins (enzymes) encoded by genes participate determine the complex specificity of the phenotypic manifestation of the trait. The degree of expression of a trait in a phenotype is called expressiveness (the term was introduced by N.V. Timofeev-Resovsky in 1927). It is understood as the degree of phenotypic manifestation of the allele in different individuals. If there are no options for the manifestation of a sign, they speak ofconstant expressiveness. For example, the alleles of the AB0 blood group systems in humans have almost constant expressivity, and the alleles that determine eye color in humans - variable expressiveness. A classic example of variable expressivity is the manifestation of a recessive mutation that reduces the number of eye facets in Drosophila: different individuals can develop a different number of facets up to complete disappearance.

Expressiveness is expressed quantitatively.The frequency of occurrence of a given trait in a generation is called penetrance (the term was proposed by N.V. Timofeev-Ressovsky in 1927). It is expressed quantitatively as a percentage. Penetrance can be complete (100% occurrence of the trait) or incomplete (occurrence of the trait is less than 100%). For example, in humans, the penetrance of congenital hip dislocation is 25%, and the penetrance of the eye defect “coloboma” is about 50%.

Knowledge of the mechanisms and nature of expressivity is important in medical genetic counseling and determining the possible genotype of phenotypically “healthy” people whose relatives had hereditary diseases. The phenomena of expressivity indicate that dominance (the manifestation of a dominant allelic gene) can be controlled, reasonably searching for means to prevent the development of hereditary anomalies and pathologically burdened heredity in humans. The fact that the same genotype can be the source of the development of different phenotypes is of significant importance for medicine. It means that burdened heredity does not necessarily have to manifest itself in a developing organism. In some cases, the development of the disease can be prevented, in particular by diet or medications.

Known identical changes in phenotype caused by changes in alleles of different genes - genocopies. Their occurrence is a consequence of the control of the trait by many genes. Since the biosynthesis of molecules in a cell, as a rule, is carried out in multisteps, mutations of different genes that control different stages of one biochemical pathway can lead to the same result - the absence of the final product of the chain of reactions and, therefore, the same change in phenotype. Thus, in humans, several forms of deafness are known, caused by mutant alleles of three autosomal genes and one gene of the X chromosome. However, in various cases, deafness is accompanied by either retinitis pigmentosa, goiter, or abnormalities in cardiac function. The problem of gene copies is also relevant in medical genetics for predicting the possible manifestation of hereditary diseases in descendants if the parents had similar diseases or developmental anomalies.

Of 23 pairs human chromosomes 22 pairs do not differ between females and males and are called autosomes. The inheritance of traits caused by genes located on autosomes does not depend on sex and is not sex-linked. The 23rd pair of chromosomes determines the sex of the individual: in women, both chromosomes of the 23rd pair (sex chromosomes) are the same - they are called X chromosomes; in men, the 23rd pair consists of one X and one Y chromosome. Accordingly, the eggs formed in oogenesis are identical in the set of chromosomes - they contain 22 autosomes and one X chromosome.

Sperm they may contain, in addition to 22 autosomes, either an X or a Y chromosome. In the first case, during fertilization, the X and X chromosomes will unite, determining the female sex of the zygote; in the second, the X and Y chromosomes will unite, giving the male sex. The human Y chromosome does not contain genes allelic to the genes of the X chromosome, therefore, in males, the genes of the X chromosome are always externally manifested, regardless of whether they are dominant or recessive (hemizygosity). In females, the manifestation of genes linked to the X chromosome is the same as in the case of autosomal genes.
Types of gene inheritance located on autosomes and X chromosomes are called autosomal and X-linked, respectively.

Thus, taking into account the localization of genes and dominance relationships, we can distinguish four main types of inheritance:
1) autosomal dominant;
2) autosomal recessive;
3) linked to the X chromosome, dominant;
4) linked to the X chromosome, recessive.

Identifying these types of inheritance based on pedigrees and constitutes the task of genealogical analysis.
Some genes, localized on autosomes, can exert their effect to varying degrees depending on gender - differently in men or women. If one sex is predominantly affected, it is referred to as sex-limited inheritance. For example, such inheritance is observed in gout and presenile alopecia, which predominantly affect men. This selectivity of the lesion is explained by the action of androgens (male sex hormones). Hippocrates also noted that “eunuchs do not get gout and do not become bald.” In another syndrome inherited as limited by sex, testicular feminization syndrome, a female phenotype is formed with a male karyotype (46, XY), which is caused by a gene mutation leading to abnormalities in the androgen receptors. And although the gene is localized in the autosome, only men suffer from this disease.

Features hereditary traits are their different expressiveness and penetrance. These terms were proposed by our outstanding geneticist N.V. Timofeev-Resovsky in 1925.

Penetrance is the frequency or probability of a gene being expressed. Penetrance can be complete or incomplete. Full penetrance is said to exist if a dominant gene in a heterozygous state or a recessive gene in a homozygous state appears in every person in whose genotype they occur. In some families with a dominant trait, there are sometimes “skipping” generations, i.e. Some individuals of a given generation have the gene, but it does not manifest itself phenotypically. In such cases, they speak of incomplete penetrance of the gene. These phenomena depend both on a person’s genotype and on the influence of the environment in which he lives. The probability of manifestation of a gene is often expressed as a percentage of cases out of the number of carriers. Complete penetrance is 100%. For a number of diseases it is quite high: for retinoblastoma - 80%, for Gardner's syndrome - 84%, for otosclerosis - 40%.

For rate penetrance The so-called three-generation chain method (in three generations) can be used, especially in the presence of large pedigrees. For this purpose, all three-generation families descending from patients with an autosomal dominant disease and having the patient in the 3rd generation are taken into account, but so that they do not have common intermediate ancestors.

Counting proportion of intermediate ancestors, in which the disease manifested itself, and is correlated with the total number of ancestors, resulting in a penetrance estimate, which is also expressed as a percentage. Penetrance is a very important concept with great practical significance. Knowing the penetrability, it is possible to state with a high degree of probability the presence or absence of the disease in the subject. Carriage of a dominant gene without pronounced signs of the disease in one of the parents can be assumed when cases of a dominant disease are found in his offspring (“generation skip”).