The concept of gene expressivity and penetrance. The importance of the unity of the external and internal environment in the development of the organism

These concepts were first introduced in 1926 by N.V. Timofeev Ressovsky and 0. Vogt to describe the varying manifestation of traits and the genes that control them. Expressiveness is the degree of expression (variation) of the same trait in different individuals who have the gene that controls this trait. Low and high expressiveness are observed. Consider, for example, the different severity of rhinitis (runny nose) in three different patients (A, B and C) with the same diagnosis of RVI. In patient A, rhinitis is mild ("sniffing"), allowing one to get by with just a handkerchief during the day; in patient B, rhinitis is moderately expressed (2-3 handkerchiefs daily); Patient C has a high degree of severity of rhinitis (5-6 handkerchiefs). When they talk about the expressiveness of not a single symptom, but the disease as a whole, doctors often assess the patient’s condition as satisfactory or of moderate severity, or as severe,

those. in this case, the concept of expressiveness is similar to the concept of “severity of the disease.”

Penetrance- this is the probability of manifestation of the same trait in different individuals who have the gene that controls this trait. Penetrance is measured as the percentage of individuals with a certain trait out of the total number of individuals who are carriers of the gene that controls the trait. 0 can be incomplete or complete.

An example of a disease with incomplete penetrance is the same rhinitis with 0RVI. So, we can assume that patient A does not have rhinitis (but there are other signs of the disease), while patients B and C do have rhinitis. Therefore, in this case, the penetrance of rhinitis is 66.6%.

An example of a disease with complete penetrance - autosomal dominant Huntington's chorea(4p16). 0na manifests mainly in people aged 31-55 years (77% of cases), while in other patients it occurs at other ages: both in the first years of life and at 65, 75 years or more. It is important to emphasize: if the gene for this disease is passed on to a descendant from one of the parents, then the disease will necessarily manifest itself, which is what complete penetrance is. True, the patient does not always live to see the manifestation of Huntington's chorea, dying from another cause.

Genecopying and its reasons
Genocopies (lat. genocopia) are similar phenotypes formed under the influence of different non-allelic genes.
A number of signs with similar external manifestations, including hereditary diseases, can be caused by various non-allelic genes. This phenomenon is called genocopy. The biological nature of gene copies lies in the fact that the synthesis of identical substances in a cell in some cases is achieved in different ways.

In human hereditary pathology, phenocopies - modification changes - also play an important role. They are due to the fact that during development, under the influence of external factors, a trait depending on a specific genotype can change; in this case, characteristics characteristic of another genotype are copied.

That is, these are identical changes in the phenotype, caused by alleles of different genes, and also occurring as a result of various gene interactions or disruptions of various stages of one biochemical process with cessation of synthesis. Manifests itself as the effect of certain mutations that copy the action of genes or their interaction.

The same trait (group of traits) can be caused by different genetic reasons (or heterogeneity). This effect, at the suggestion of the German geneticist H. Nachtheim, was obtained in the mid-40s of the 20th century. Name gene copying. There are three known groups of reasons for gene copying.

Reasons for the first group combines heterogeneity due to polylocus, or the action of different genes located at different loci on different chromosomes. For example, among the hereditary diseases of the metabolism of complex sugars - glycosaminoglycans, 19 types (subtypes) of mucopolysaccharidoses have been identified. All types of characteristics

are characterized by defects in different enzymes, but manifest themselves with the same (or similar) symptoms gargoylic dysmorphism or the phenotype of the bell ringer Quasimodo - the main character of the novel “Notre Dame Cathedral” by the classic of French literature Victor Hugo. A similar phenotype is often observed in mucolipidoses (lipid metabolism disorders).

Another example of polylocus is phenylketonuria. Now not only its classic type, caused by a deficiency of phenylalanine-4-hydroxylase (12q24.2), has been identified, but also three atypical forms: one caused by a deficiency of dihydropteridine reductase (4p15.1), and two more by a deficiency of the enzymes pyruvoyltetrahydropterin synthetase and tetrahydrobiopterin (corresponding genes have not yet been identified).

Additional examples of polylocus: glycogenosis (10 genocopies), Ellers-Danlos syndrome (8), Recklinghausen neurofibramatosis (6), congenital hypothyroidism (5), hemolytic anemia (5), Alzheimer's disease (5), Bardet-Biedl syndrome (3), breast cancer (2).

Reasons for the second group united by intralocus heterogeneity. It is caused either by multiple allelism (see Chapter 2) or by the presence genetic compounds, or double heterozygotes, having two identical pathological alleles at identical loci of homologous chromosomes. An example of the latter is heterozygous beta thalassemia (11p15.5), which is formed as a result of deletions of two genes encoding the beta chains of globins, which leads to an increased content of hemoglobin HbA 2 and an increased (or normal) level of hemoglobin HbF.

Reasons for the third group combines heterogeneity due to mutations at different points of the same gene. An example is cystic fibrosis (7q31-q32), which develops due to the presence of almost 1000 point mutations in the gene responsible for the disease. Given the total length of the cystic fibrosis gene (250 thousand bp), up to 5000 such mutations are expected to be found in it. This gene encodes a protein responsible for the transmembrane transport of chlorine ions, which leads to an increase in the viscosity of the secretions of the exocrine glands (sweat, salivary, sublingual, etc.) and blockage of their ducts.

Another example is classical phenylketonuria, caused by the presence of 50 point mutations in the gene encoding phenylalanine 4-hydroxylase (12q24.2); In total, more than 500 point mutations of the gene are expected to be detected in this disease. Most of them arise from polymorphisms in restriction fragment length (RFLP) or number of tandem repeats (VNTP). It has been established: the main mutation of the phenylketonuria gene in Slavic populations is R408 W/

Pleiotropy effect

The above-mentioned ambiguity in the nature of the relationships between genes and traits is also expressed in pleiotropy effect or pleiotropic action, when one gene causes the formation of a number of traits.

For example, the autosomal recessive ataxia-telangiectasia gene, or Louis-Bar syndrome(11q23.2) is responsible for simultaneous damage to at least six body systems (nervous and immune systems, skin, mucous membranes of the respiratory and gastrointestinal tract, as well as the conjunctiva of the eyes).

Other examples: gene Bardet-Biedl syndrome(16q21) causes dementia, polydactyly, obesity, pigmentary degeneration of the retina; Fanconi anemia gene (20q13.2-13.3), which controls the activity of topoisomerase I, causes anemia, thrombocytopenia, leukopenia, microcephaly, aplasia of the radius, hypoplasia of the metacarpal bone of the first finger, malformations of the heart and kidneys, hypospadias, pigment spots of the skin, increased fragility of chromosomes .

There are primary and secondary pleiotropy. Primary pleiotropy is caused by the biochemical mechanisms of action of the mutant enzyme protein (for example, phenylalanine-4-hydroxylase deficiency in phenylketonuria).

Secondary pleiotropy caused by complications of the pathological process that developed as a result of primary pleiotropy. For example, due to increased hematopoiesis and hemosiderosis of parenchymal organs, thickening of the skull bones and hepatolienal syndrome occur in a patient with thalassemia.

A gene present in the genotype in the quantity required for manifestation (1 allele for dominant traits and 2 alleles for recessive traits) can manifest itself as a trait to varying degrees in different organisms (expressiveness) or not manifest itself at all (penetrance).

Modification variability (impact of environmental conditions)

Combinative variability (impact of other genes of the genotype).

Expressiveness– degree of phenotypic manifestation of the allele. For example, alleles of blood groups AB0 in humans have constant expressivity (they are always 100% expressed), and alleles that determine eye color have variable expressivity. A recessive mutation that reduces the number of eye facets in Drosophila reduces the number of facets in different ways in different individuals, up to their complete absence.

Expressiveness reflects the nature and severity of symptoms, as well as the age of onset of the disease.

If a person suffering from a dominant disease wants to know how severe the disease will be in his child who has inherited the mutation, then he raises the question of expressivity. Using gene diagnostics, it is possible to identify a mutation that does not even manifest itself, but it is impossible to predict the range of expression of the mutation in a given family.

Variable expressivity, up to the complete absence of expression of the gene, can be due to:

The influence of genes located in the same or other loci;

Exposure to external and random factors.

Penetrance– the probability of the phenotypic manifestation of a trait in the presence of the corresponding gene. For example, the penetrance of congenital hip dislocation in humans is 25%, i.e. Only 1/4 of recessive homozygotes suffer from the disease. Medical-genetic significance of penetrance: a healthy person, whose one of the parents suffers from a disease with incomplete penetrance, may have an undetected mutant gene and pass it on to his children.

It is determined by the percentage of individuals in the population carrying the gene in which it manifests itself. With complete penetrance, a dominant or homozygous recessive allele appears in each individual, and with incomplete penetrance, in some individuals.

Penetrance may be important in medical genetic counseling in the case of autosomal dominant diseases. A healthy person, whose one of the parents suffers from a similar disease, from the point of view of classical inheritance, cannot be a carrier of the mutant gene. However, if we take into account the possibility of incomplete penetrance, the picture is completely different: an apparently healthy person can have an undetected mutant gene and pass it on to children.

Gene diagnostic methods make it possible to determine whether a person has a mutant gene and to distinguish a normal gene from an undetected mutant gene.

In practice, the determination of penetrance often depends on the quality of the research methods; for example, MRI can detect symptoms of a disease that were not previously detected.

From a medical point of view, a gene is considered to be manifested even in an asymptomatic disease if functional deviations from the norm are identified. From a biological point of view, a gene is considered expressed if it disrupts the functions of the body.

Polygenic inheritance

Polygenic inheritance– inheritance in which several genes determine the manifestation of one trait.

Complementarity- an interaction of genes in which 2 or more genes cause the development of a trait. For example, in humans, the genes responsible for the synthesis of interferon are located on chromosomes 2 and 5. In order for the human body to produce interferon, it is necessary that at least one dominant allele be present simultaneously on both chromosomes 2 and 5. Let us designate the genes associated with the synthesis of interferon and located on chromosome 2 as A (a), and on chromosome 5 as B (c). The options AABB, AaBB, AAVv, AaBv will correspond to the body’s ability to produce interferon, and the options aaBB, AAbb, aaBB, Aavv, aaBv will correspond to the inability.

A type of inheritance of traits caused by the action of many genes, each of which has only a weak effect. Phenotypically, the manifestation of a polygenically determined trait depends on environmental conditions. In descendants, a continuous series of variations in the quantitative manifestation of such a trait is observed, rather than the appearance of classes clearly distinguished by phenotype. In some cases, when a single gene is blocked, the symptom does not appear at all, despite its polygenic nature. This indicates a threshold manifestation of the trait.

Since the development of polygenic traits is greatly influenced by environmental factors, identifying the role of genes in these cases is difficult.

Polymerism- several genes act on one trait in the same way. Moreover, when forming a trait, it does not matter which pair the dominant alleles belong to, what is important is their number.

For example, the color of human skin is influenced by a special substance - melanin, the content of which provides a color palette from white to black (except for red). The presence of melanin depends on 4-5 pairs of genes. To simplify the problem, we will conventionally assume that there are two such genes. Then the black genotype can be written - AAAA, the white genotype - aaaa. Light-skinned blacks will have the genotype AAAa, mulattoes - AAaa, light mulattoes - Aaaa.

Pleiotropy- the influence of one gene on the appearance of several traits. An example is an autosomal dominant disease from the group of hereditary connective tissue pathologies. In classic cases, individuals with Marfan syndrome are tall (dolichostenomelia), have elongated limbs, elongated fingers (arachnodactyly), and underdeveloped fat tissue. In addition to characteristic changes in the organs of the musculoskeletal system (elongated tubular bones of the skeleton, hypermobility of joints), pathology is observed in the organs of vision and the cardiovascular system, which in classical versions constitutes the Marfan triad.

Without treatment, the life expectancy of people with Marfan syndrome is often limited to 30-40 years and death occurs due to dissecting aortic aneurysm or congestive heart failure. In countries with developed healthcare, patients are successfully treated and live to an old age. Among famous historical figures, this syndrome manifested itself in A. Lincoln, N. Paganini, K.I. Chukovsky (Fig. 3.4, 3.5).

Epistasis- suppression by one gene of another, non-allelic. An example of epistasis is the “Bombay phenomenon”. In India, families are described in which the parents had the second (AO) and first (00) blood groups, and their children had the fourth (AB) and first (00). In order for a child in such a family to have blood group AB, the mother must have blood group B, but not O. It was found that in the ABO blood group system there are recessive modifier genes that suppress the expression of antigens on the surface of red blood cells, and phenotypically manifests itself in humans blood type O.

Another example of epistasis is the appearance of white albinos in a black family. In this case, the recessive gene suppresses the production of melanin, and if a person is homozygous for this gene, then no matter how many dominant genes responsible for the synthesis of melanin he has, his skin color will be albiotic (Fig. 3.6).

Morris syndrome- androgen insensitivity syndrome (testicular feminization syndrome) is manifested by disorders of sexual development that develop as a result of a weak response to male sex hormones in individuals with a male set of chromosomes (XY). American gynecologist John Morris was the first to coin the term “testicular feminization syndrome” in 1953.

This syndrome is the most well-known cause of a man developing as a girl or the presence of manifestations of feminization in boys who were born with a male set of chromosomes and normal levels of sex hormones. There are two forms of androgen insensitivity: complete or partial insensitivity. Children with the complete form of insensitivity have a uniquely female appearance and development, while those with the partial form may have a combination of female and male external sexual characteristics, depending on the degree of androgen insensitivity. The incidence rate is approximately 1-5 per 100,000 newborns. Partial androgen insensitivity syndrome is more common. Complete insensitivity to male sex hormones is a very rare disease.

The disease is caused by a mutation in the AL gene on the X chromosome. This gene determines the function of androgen receptors, a protein that responds to signals from male sex hormones and triggers a cellular response. In the absence of androgen receptor activity, the development of male genital organs will not occur. Androgen receptors are necessary for the development of pubic and axillary hair, regulate beard growth and the activity of sweat glands. With complete androgen insensitivity, there is no androgen receptor activity. If some cells have a normal number of active receptors, then this is partial androgen insensitivity syndrome.

The syndrome is inherited on the X chromosome as a recessive trait. This means that the mutation causing the syndrome is located on the X chromosome. According to some information, in particular the study of the reasons for the genius of V.P. Efroimson, Joan of Arc had Morris syndrome.

Pleiotropic action of genes

Pleiotropic action of genes- this is the dependence of several traits on one gene, that is, the multiple effects of one gene.

In Drosophila, the gene for white eye color simultaneously affects the color of the body, length, wings, structure of the reproductive apparatus, reduces fertility, and reduces life expectancy. A hereditary disease is known in humans - arachnodactyly ("spider fingers" - very thin and long fingers), or Marfan's disease. The gene responsible for this disease causes a disorder in the development of connective tissue and simultaneously affects the development of several signs: disruption of the structure of the eye lens, abnormalities in the cardiovascular system.

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The term “penetrance” was introduced by Timofeev-Ressovsky. This concept refers to the ability of genes to manifest themselves in a genotype; and is expressed as the quotient of the number of individuals with a trait divided by the total number of individuals having the gene for this trait. Examples of penetrance are: the color of the Chinese primrose flower depends on air temperature; signs of 100% penetrance - blood type, right-handedness.

Expressiveness is the degree of manifestation of a trait. Both properties depend on external conditions. Examples of expressivity are: the elony gene (“e//e” homozygote) - black body color in Drosophila; gray body color (“+//+” homozygote); if the temperature is less than 20°, then a dark gray color (“+//e” heterozygote); if more than 20°, then gray (“+//e” heterozygote); Thus, low temperature indicates the predominance of recessive genes, and high temperature indicates the predominance of semi-dominant genes.

Multiple allelism.

If a gene has a large number of alleles, then this group is called a series of alleles. A series of alleles of the gene responsible for eye color in Drosophila has been established: the mutation of white eyes (white - white (I chromosome)).

P w//w (white) x wa// (apricot)

F1 w//wa(light yellow - compound); w// (white)

Individuals are heterozygotes for a given gene (compound). The compound does not show a return to the wild type; they (individuals) have an intermediate manifestation of characteristics. The absence of reversion to the wild type is a diagnostic sign of the allelicity of these mutations.

wa//wa - chromosome I (apricot)

+//+ - Chromosome III (apricot)

+//+ - I chromosome (bright)

st//st - chromosome III (bright)

wa and st - non-allelic characters

And + - wild type

C > ch > cch > albino

Wild Himalayan albino chinchilla

C x sa - wild form

Buckwheat and tobacco have genes responsible for the incompatibility of stigma and pistil:

C1 C2 C3 C4 C5…

Р С1С2 x С1С2 Р С1С2 x С1С3

self-pollination impossible partial sterility

PENETRANCE PENETRANCE

(from Latin penetrans, genus penetrantis - penetrating, reaching), the frequency of manifestation of the allele of a certain gene in different individuals of a related group of organisms. The term "P." proposed in 1927 by N.V. Timofeev-Resovsky. A distinction is made between complete P. (the allele is manifested in all individuals) and incomplete P. (the allele does not manifest in some individuals). P. is expressed quantitatively as a percentage of individuals in which this allele is manifested (100% - complete P.). Incomplete P. is characteristic of the manifestation of plural. genes. For example, in humans P. congenital dislocation of the hip is 25%, P. eye defect - coloboma - approx. 50%. Incomplete P. may be based on both genetic factors. reasons and external influence. conditions. Knowledge of the mechanisms of P. and the nature of P. of certain alleles is important in medical genetics. counseling and determining the possible genotype of “healthy” people whose relatives had inheritances or diseases. Special cases of incomplete P. can be considered the manifestation of genes that control sex-limited traits (for example, plumage color, egg production, fat milk production), as well as sex-dependent traits. For example, an allele of a gene that causes baldness in men heterozygous for this allele does not appear in heterozygous women. When homozygous, this allele causes baldness in men and thinning hair in women. (see EXPRESSIVENESS).

.(Source: “Biological Encyclopedic Dictionary.” Editor-in-chief M. S. Gilyarov; Editorial Board: A. A. Babaev, G. G. Vinberg, G. A. Zavarzin and others - 2nd ed., corrected . - M.: Sov. Encyclopedia, 1986.)

See what “PENETRANCE” is in other dictionaries:

- (population genetics) an indicator of the phenotypic manifestation of an allele in a population. It is defined as the ratio (usually as a percentage) of the number of individuals in which phenotypic manifestations of the presence of the allele are observed to the total number of individuals in ... ... Wikipedia

- (from the Latin penetrans genus penetrantis penetrantis), the frequency of manifestation of a gene, determined by the number of individuals (within a related group of organisms) that exhibit a trait controlled by a given gene... Big Encyclopedic Dictionary

Penetrance. See gene expression. (Source: “English-Russian Explanatory Dictionary of Genetic Terms.” Arefiev V.A., Lisovenko L.A., Moscow: Publishing House VNIRO, 1995) ... Molecular biology and genetics. Explanatory dictionary.

- (from Latin penetro I penetrate, I reach), the frequency with which a dominant or recessive gene in a homozygous state manifests itself phenotypically. The term was introduced by N.V. Timofeev Resovsky (1927). Ecological encyclopedic dictionary. Chisinau: Home… … Ecological dictionary

penetrance- and, f. penétrance f. Biol. sl. 377... Historical Dictionary of Gallicisms of the Russian Language

penetrance- gene manifestation The frequency of manifestation of a particular allele in a group of related organisms (the degree of its manifestation in an individual is called expressivity); with complete P., the allele is manifested in all individuals in the sample, the majority... ... Technical Translator's Guide

Penetrance- * penetrance * penetrance frequency or probability of manifestation of a gene (allele) in a group of related organisms under appropriate environmental conditions. P. is determined by the proportion of individuals (in%) carriers of the gene (allele) being studied in which it... ... Genetics. Encyclopedic Dictionary

PENETRANCE- (repetrance) the frequency with which a given trait is controlled by a particular gene. Full penetrance is observed in cases where a given trait is present in all individuals whose bodies contain a particular gene. If... ... Explanatory dictionary of medicine

- (from Latin penetrans, genus penetrantis penetrantis), frequency of gene manifestation, determined by the number of individuals (within a related group of organisms) in which a trait controlled by a given gene manifests itself. * * * PENETRANCE… … Encyclopedic Dictionary

- (from Latin penetro I penetrate, I reach) a quantitative indicator of the phenotypic variability of gene manifestation. It is measured (usually in %) by the ratio of the number of individuals in which a given Gene manifested itself in the Phenotype to the total number of individuals in the Genotype... ... Great Soviet Encyclopedia

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 (P_) 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 length of the day 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.