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Expressivity and penetrance are examples. Penetrance, expressivity, norm of gene reaction. Unusual Aspects of Inheritance

Pleiotropy), multiple action of a gene, the ability of one hereditary factor - a gene - to simultaneously influence several different characteristics of the body. In the initial period of the development of Mendelism, when no fundamental distinction was made between genotype and phenotype, the prevailing idea was the unambiguous action of the gene (“one gene - one trait”). However, the relationship between gene and trait turned out to be much more complex. Even G. Mendel discovered that one hereditary factor in pea plants can determine various characteristics: the red color of the flowers, the gray color of the seed coat and the pink spot at the base of the leaves. Subsequently, it was shown that the manifestation of a gene can be diverse and that almost all well-studied genes are characterized by P., i.e., each gene acts on the entire system of the developing organism, and any hereditary trait is determined by many genes (in fact, the entire genotype). Thus, the genes that determine the coat color of the house mouse. influence body size; the gene that affects eye pigmentation in the mill moth has 10 more morphological and physiological manifestations, etc. P. often extends to traits of evolutionary significance—fertility, life expectancy, and the ability to survive in extreme environmental conditions. In Drosophila, many studied mutations affect viability (for example, the white-eyed gene also affects the color and shape of internal organs, reduces fertility, and reduces life expectancy).

Expressiveness, the severity of the phenotypic manifestation of genes. Some genes in animals, plants, and microorganisms are characterized by relatively constant E., that is, they manifest themselves approximately equally in all individuals of the corresponding genotype. For example, on all wheat plants that are homozygous for the gene causing the absence of awns, awnless ears develop. Other genes (and they are, apparently, the majority) are distinguished by changing E. In rabbits and some other animals, there is a known recessive gene for the Himalayan (“ermine”) coloration, which causes a peculiar spotted fur (on a white or light background the tips of the paws, ears, muzzle and tail are black). However, this coloration develops only when young Himalayan breeds are raised at moderate temperatures. At elevated temperatures, all fur of individuals of the same Himalayan genotype turns out to be white, and at lower temperatures, it turns out to be black. This example indicates that E. is influenced by environmental factors, in this case temperature. Under the same environmental conditions, the E. gene can vary depending on the genotypic environment, that is, on what other genes the given gene is part of the genotype in combination with. The role of modifier genes in E. variation is indicated by the possibility in a number of cases of stabilizing art, selection for one or another degree of expression of hereditary characteristics in the phenotype. E . and penetrance are the main interrelated indicators of phenotypic variability of gene expression, widely used in phenogenetics, medical genetics, breeding of animals, plants and microorganisms

Penetrance a quantitative indicator of phenotypic variability in gene expression. 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 whose genotype this gene is present in the state necessary for its manifestation (homozygous - in the case of recessive genes or heterozygous - in the case of dominant genes) . The manifestation of a gene in 100% of individuals with the corresponding genotype is called complete P., in other cases - incomplete P. Incomplete P. is characteristic of the manifestation of many genes in humans, animals, plants and microorganisms. For example, some hereditary human diseases develop only in a portion of individuals whose genotype contains an abnormal gene; for the rest, the hereditary predisposition to the disease remains unrealized. Incomplete gene generation is due to the complexity and multi-stage nature of processes occurring from the primary action of genes at the molecular level to the formation of final characteristics at the level of the entire organism. P. gene can vary widely depending on the genotypic environment. Through selection, it is possible to obtain lines of individuals with a given level of P. The average level of P. also depends on environmental conditions.

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Penetrance is the frequency of expression of a gene. 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.

Expressivity is the degree of phenotypic manifestation of a gene as a measure of the strength of its action, determined by the degree of development of the trait. Expressivity can be influenced by modifier genes and environmental factors. In mutants with incomplete penetrance, expressivity often changes. Penetrance is a qualitative phenomenon, expressiveness is quantitative.

In medicine, penetrance is the proportion of people with a given genotype who have at least one symptom of a disease (in other words, penetrance determines the likelihood of a disease, but not its severity). Some believe that penetrance changes with age, such as in Huntington's disease, but differences in age of onset are usually attributed to variable expressivity. Penetrance is sometimes influenced by environmental factors, such as G6PD deficiency.

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.

Although it is common to speak of penetrance and expressivity in autosomal dominant diseases, the same principles apply to chromosomal, autosomal recessive, X-linked, and polygenic diseases.

The development of the embryo proceeds through the continuous interaction of hereditary and external factors. In the process of such relationships, a phenotype is formed, which actually reflects the result of the implementation of the hereditary program in specific environmental conditions. Despite the fact that the intrauterine development of the embryo in mammals occurs in a relatively constant environment under optimal conditions, the influence of external unfavorable factors during this period is not at all excluded, especially with their increasing accumulation in the environment due to technological progress. Currently, a person is exposed to chemical, physical, biological and psychological factors at all periods of his life.

Experimental studies of animal development have led to the idea of ​​so-called critical periods in the development of organisms. This term refers to periods when the embryo is most sensitive to the damaging effects of various factors that can disrupt normal development, i.e. These are periods of least resistance of the embryo to environmental factors.

Protein synthesis largely determines body structure and function.

Structure

Humans have about 20,000 genes. Genes are contained on chromosomes in the cell nucleus and mitochondria. In humans, the somatic (nongerm) cell nuclei, with some exceptions (eg, red blood cells), typically have 46 chromosomes organized into 25 pairs. Each pair consists of 1 chromosome from the mother and 1 from the father. 22 pairs of 23 - a y-tosome - are usually homologous (identical in size, shape, location and number of genes). The 23rd pair of sex chromosomes (X and Y) determines the sex of a person. Women have 2 X chromosomes (which are homologous) in the nuclei of somatic cells; males have 1 X and 1 Y chromosome (which are heterologous). The Y chromosome contains genes responsible for sexual differentiation along with other genes. Because the X chromosome has many more genes than the Y chromosomes, many genes on the X chromosome are unpaired in males. A karyotype is the complete set of chromosomes in human cells.

Embryonic cells (eggs and sperm) undergo meiosis, which reduces the number of chromosomes to 25 - half the number in somatic cells. In meiosis, the genetic information inherited by a person from his mother and father is recombined through crossing over (exchange between homologous chromosomes). When an egg is fertilized by sperm at conception, the normal number of 46 chromosomes is restored.

Genes are arranged in a linear sequence along the DNA in chromosomes; each gene has its own location, completely identical in each of the 2 homologous chromosomes. Genes that occupy the same loci on each chromosome of a pair (1 inherited from the mother and 1 from the father) are called alleles. Each gene consists of a specific DNA sequence; 2 alleles can have several different DNA sequences. Possessing a pair of identical alleles for a particular gene means homozygosity; Possession of a pair of non-identical alleles is heterozygosity.

Gene functions

Genes are made of DNA. The length of a gene depends on the length of the protein that the gene encodes. DNA is a double helix in which the nucleotides (bases) are paired; adenine (A) is paired with thymine (T), and guanine (G) is paired with cytosine (C). DNA is transcribed during protein synthesis. When DNA reproduces itself during cell division, 1 strand of DNA is used as a template from which messenger RNA (mRNA) is made. RNA has the same base pairs as DNA, except that uracil (U) replaces thymine (T). Parts of the mRNA travel from the nucleus to the cytoplasm and then to the ribosome, where protein synthesis occurs. Transfer RNA (tRNA) carries each amino acid to the ribosome, where it is added to the growing polypeptide chain in the sequence specified by the mRNA. Once a chain of amino acids is assembled, it folds to create a complex 3-dimensional structure under the influence of neighboring chaperone molecules.

The DNA code is written in triplets of 4 possible nucleotides. Specific amino acids are encoded by specific triplets. Since there are 4 nucleotides, the number of possible triplets is 43 (64). Since there are only 20 amino acids, additional combinations of triplets exist. Some triplets encode the same amino acids as other triplets. Other triplets may encode elements such as the instruction to start or stop protein synthesis and the order in which amino acids join and line up.

Genes consist of exons and introns. Exons encode the amino acid components of the finished protein. Introns contain other information that influences the control and rate of protein production. Exons and introns are transcribed together into mRNA, but the segments transcribed from the introns are later excised. Transcription is also controlled by antisense RNA, which is synthesized from strands of DNA that are not transcribed into mRNA. Chromosomes are made up of histones and other proteins that influence gene expression (which proteins and how many proteins are synthesized from a given gene).

Genotype refers to genetic makeup and determines which proteins are coded for production. Phenotype refers to the entire physical, biochemical and physiological makeup of a person, i.e., how the cell (and thus the organism as a whole) functions. The phenotype is determined by the types and amounts of protein synthesized, i.e. how genes are actually expressed. Gene expression depends on factors such as whether the trait is dominant or recessive, gene penetrance and expressivity, degree of tissue differentiation (determined by tissue type and age), environmental factors, unknown factors, and whether expression is sex-limited or subject to chromosomal inactivation or genomic imprinting. Factors that influence gene expression without changing the genome are epigenetic factors.

Knowledge of the biochemical mechanisms that mediate gene expression is growing rapidly. One mechanism is variation in intron splicing (also called alternative splicing). Because introns are cut during splicing, exons can also be cut and then exons can be assembled in many combinations, resulting in many different mRNAs being able to encode similar but different proteins. The number of proteins that can be synthesized by humans exceeds 100,000, although the human genome has only about 20,000 genes. Other mechanisms mediating gene expression include DNA methylation and histone reactions such as methylation and acetylation. DNA methylation tends to silence a gene. Histones are like spools around which DNA is wound. Histone modifications, such as methylation, can increase or decrease the amount of proteins synthesized from a particular gene. Histone acetylation is associated with decreased gene expression. The DNA strand that is not transcribed to form mRNA can also be used as a template for the synthesis of RNA, which controls the transcription of the opposite strand.

Traits and patterns of inheritance

The sign can be as simple as eye color or as complex as susceptibility to diabetes. A defect in one gene can cause abnormalities in multiple organ systems. For example, osteogenesis imperfecta (a connective tissue disorder often caused by abnormalities in the genes encoding collagen synthesis) can cause bone weakness, deafness, bluish whites of the eyes, dental dysplasia, hypermobile joints, and heart valve abnormalities.

Construction of family genealogy. Family genealogy (family tree) can be represented as a graphical representation of inheritance patterns. It is also widely used in genetic counseling. Family genealogy uses common symbols to represent family members and related information about their health. Some familial disorders with the same phenotypes have multiple inheritance patterns.

Single gene defects

If the expression of a trait requires only one copy of a gene (1 allele), that trait is considered dominant. If expression of a trait requires two copies of a gene (2 alleles), the trait is considered recessive. The exception is X-linked diseases. Since males do not usually have paired alleles to compensate for the effects of most alleles on the X chromosome, the X chromosome allele is expressed in males even if the trait is recessive.

Many specific diseases have been previously described.

Factors influencing gene expression

Many factors can influence gene expression. Some of them cause the expression of traits to deviate from the patterns predicted by Mendelian inheritance.

Penetrance and expressivity. Penetrance is a measure of how often a gene is expressed. It is defined as the percentage of people who have the gene and who develop the corresponding phenotype. A gene with incomplete (low) penetrance cannot be expressed even when the trait is dominant or when it is recessive and the gene responsible for the trait is present on both chromosomes. The penetrance of the same gene may vary from person to person and may depend on the age of the person. Even when abnormal alleles are not expressed (non-penetrance), a healthy carrier of the abnormal allele can pass it on to children who may develop clinical abnormalities. In such cases, the gender verbatim skips the generation. However, some cases of apparent nonpenetrance are due to the examiner's ignorance or failure to recognize minor manifestations of the disease. Patients with minimal expression are sometimes thought to have a variant of the disease.

Expressivity is the extent to which a gene is expressed in one individual. It can be classified as a percentage; for example, when a gene is 50% expressive, only half the function is present or the severity is only half of what would occur with full expression. Expressivity can be influenced by the environment and other genes, so individuals who share the same gene may vary in phenotype. Expressiveness can vary even among members of the same family.

Sex-linked inheritance. A trait that appears only in one sex is called sex-linked. Sex-limited inheritance, perhaps more properly called sex-biased inheritance, refers to special cases in which sex hormones and other physiological differences between men and women alter the expressivity and penetrance of a gene. For example, premature baldness (known as male pattern baldness) is an autosomal dominant trait, but such baldness is rarely expressed in women, and then usually only after menopause.

Genomic imprinting. Genomic imprinting is the differential expression of genetic material depending on whether it was inherited from the father or mother. Most autosomes express both parental and maternal alleles. However, in less than 1% of alleles, expression is possible only from the paternal or maternal allele. Genomic imprinting is usually determined by effects

which can occur in the development of gametes. Changes such as DNA methylation can cause certain maternal or paternal alleles to be expressed to varying degrees. The disease can apparently skip a generation if genomic imprinting prevents expression of the disease-causing allele. Defective imprinting, such as atypical activation or silencing of alleles, can lead to diseases.

Codominance. Both co-dominant alleles are observed. Thus, the phenotype of heterozygotes is different from that of any homozygote. For example, if a person has 1 allele coding for blood type A and 1 allele coding for blood type B, the person will have blood of both types (blood type AB).

Chromosome inactivation. In women who have more than 1 X chromosome (except eggs), all but one of the X chromosomes is inactivated; those. most alleles on the chromosome are not expressed. Inactivation occurs individually in each cell at the beginning of intrauterine life, sometimes the X chromosome from the mother is inactivated, and sometimes the X chromosome from the father. Sometimes most of the X chromosome inactivation comes from one of the parents, called skewed X chromosome inactivation. In any case, once inactivation has occurred in a cell, all descendants of that cell have the same X chromosome inactivation.

However, some alleles are expressed on the inactive X chromosome. Many of these alleles are found on chromosomal regions that correspond to regions of the Y chromosome (and are thus called pseudoautosomal regions because both men and women receive 2 copies of these regions).

Unusual Aspects of Inheritance

Some situations present aberrant inheritance, often due to changes in genes or chromosomes. However, some of these variations, such as mosaicism, are very common, others, such as polymorphisms, which are so common that they can be considered normal variants.

Mutation and polymorphism. Variations in DNA can occur spontaneously or in response to cellular damage (eg, radiation, mutagenic drugs, viruses). Some of them are repaired by cellular DNA error correction mechanisms. Others do not and can be transferred subsequently to the reproduced cells; in such cases the change is called a mutation. However, a descendant can only inherit the mutation when the germ cells are affected. Mutations may be unique to an individual or family. Most mutations are rare. Polymorphism begins as a mutation. These are changes in DNA that become common in a population (prevalence greater than 1%) due to sufficient prevalence or other mechanisms. Most of them are stable and insignificant. A typical example is human blood groups (A, B, AB and O).

Mutations (and polymorphisms) involve random changes in DNA. Most of them have little effect on cell function. Some alter cell function, usually in a harmful manner, and some are lethal to the cell. Examples of deleterious changes in cell function are mutations that cause cancer by creating oncogenes or by altering tumor suppressor genes. In rare cases, a change in cell function provides a survival advantage. These mutations are likely to spread. The mutation that causes sickle cell disease confers resistance to malaria. This resistance provides a survival advantage in areas where malaria is endemic and often fatal. However, while causing the symptoms and complications of sickle cell disease, the mutation usually also has harmful effects when present in a homozygous state.

When and in what type of cells mutations occur may explain some disturbances in the order of inheritance. Typically, an autosomal dominant disorder is expected to be present in one or both of the affected parents. However, some disorders with autosomal dominant inheritance may reappear (in people whose parents have a normal phenotype). For example, about 80% of people with achondroplastic dwarfism do not have a family history of dwarfism. In many of these individuals, the mechanism is a spontaneous mutation occurring very early in their embryonic life. Thus, other offspring do not have an increased risk of the disorder. However, in some of them the disorder develops due to mutations in the germ cells of the parents (for example, an autosomal dominant gene in phenotypically normal parents). If so, then other offspring have an increased risk of inheriting the mutation.

Mosaic. Mosaicism occurs when a person, starting from one fertilized egg, develops more than two cell lines that differ in genotype. Mosaicism is a normal consequence of X chromosome inactivation in women; in most women, some cells have inactive maternal X chromosomes and other cells have inactive paternal X chromosomes. Mosaicism can also be the result of mutation. Because these changes can be transmitted to subsequently created cells, large multicellular organisms have subclones of cells that possess several different genotypes.

Mosaicity can be recognized as the cause of disorders in which focal changes are observed. For example, Albright's syndrome is associated with patchy dysplastic changes in the bone, abnormalities of the endocrine glands, focal changes in pigmentation, and sometimes cardiac or liver dysfunction. The appearance of the Albright mutation in all cells would lead to early death, but people with mosaicism survive because normal tissue supports the abnormal tissue. Sometimes, when a parent with a monogenic disease appears to have a mild form of the disease, it is actually a mosaic; the parents' offspring are more severely affected if they receive a germ cell with the mutant allele and thus have abnormalities in every cell.

Chromosomal abnormalities are most often fatal to the fetus. However, chromosomal mosaicism is observed in some embryos, resulting in a certain number of chromosomally normal cells that enable the offspring to be born alive. Chromosomal mosaicism can be detected through prenatal genetic testing, particularly through chorionic villus sampling.

Extra or missing chromosomes. An abnormal number of autosomes usually leads to severe pathology. For example, extra autosomes usually cause disorders such as Down syndrome and other severe syndromes, or can be fatal to the fetus. The absence of an autosome is always fatal to the fetus. Chromosomal abnormalities can usually be diagnosed before birth.

Because of X chromosome inactivation, having an abnormal number of X chromosomes is generally a much less serious problem than having an abnormal number of autosomes. For example, disorders caused by the absence of one X chromosome are usually relatively minor (for example, Turner syndrome). In addition, women with three X chromosomes are often physically and mentally normal; only one X chromosome of the genetic material is fully active, even if a woman has more than two X chromosomes (the additional X chromosomes are also partially inactivated).

Uniparental disomy. Uniparental disomy occurs when both chromosomes are inherited from only one parent.

Chromosomal translocation. Chromosomal translocation is the exchange of chromosomal parts between unpaired (non-homologous) chromosomes. If chromosomes exchange equal parts of genetic material, the translocation is called balanced. An unbalanced translocation results in the loss of chromosomal material, usually the short arms of the two condensed chromosomes, leaving only 45 chromosomes; most people with translocations are phenotypically normal. However, translocations can cause or contribute to the occurrence of leukemia (acute myeloid leukemia [AML], or chronic myeloid leukemia) or Down syndrome. Translocations can increase the risk of chromosomal abnormalities in the offspring, especially unbalanced translocations. Because chromosomal abnormalities are often fatal to the embryo or fetus, parental translocations can lead to unexplained recurrent spontaneous miscarriages or infertility.

Triplet (trinucleotide) repeated violations. When the number of triplets increases sufficiently, the gene stops functioning normally. Triplet disorders are rare but cause a number of neurological disorders (eg, dystrophic myotonia, fragile X mental retardation), especially those associated with the central nervous system. Triplet repeat disorders can be detected using DNA analysis techniques.

Mitochondrial DNA mutations

The cytoplasm of each cell contains several hundred mitochondria. For practical purposes, all mitochondria are inherited from the cytoplasm of the egg, so mitochondrial DNA comes only from the mother.

Mitochondrial disorders may be associated with mutations in mitochondrial or nuclear DNA (eg, deletions, duplications, mutations). High-energy tissues (eg, muscle, heart, brain) are at particular risk due to dysfunction due to mitochondrial disorders. Specific mutations in mitochondrial DNA lead to characteristic manifestations. Mitochondrial disorders are equally common among men and women.

Mitochondrial disorders can occur in many common diseases, such as some types of Parkinson's disease (involving large mitochondrial deletion in basal ganglia cells) and many types of muscle disorders.

Patterns of maternal inheritance characterize mitochondrial DNA disorders. Thus, all descendants of sick women are at risk of inheriting anomalies.

Genetic diagnostic technologies

Genetic diagnostic technologies are rapidly improving. DNA or RNA can be amplified by using PCR to create multiple copies of a gene or gene segment.

Genetic probes can be used to search for specific segments of normal or mutated DNA. A known segment of DNA can be cloned and then labeled with a radioactive or fluorescent label; this segment is then connected to the test sample. Labeled DNA binds to its complementary DNA segment and can be detected by measuring radioactivity or the amount and type of fluorescence. Genetic probes can detect a range of diseases before and after birth. In the future, genetic probes will likely be used to test people for multiple major genetic diseases simultaneously.

Microarrays are powerful new tools that can be used to identify mutations in DNA, pieces of RNA or proteins. A single chip can test for 30,000 different DNA changes using just one sample.

Clinical applications of genetics

Understanding the disease

Genetics has contributed to a better understanding of many diseases, sometimes allowing for changes in their classification. For example, the classification of many spinocerebellar ataxias has been changed from a group based on clinical criteria to a group based on genetic criteria. Spinocerebellar ataxias (SCAs) are the major autosomal dominant ataxias.

Diagnostics

Genetic testing is used to diagnose many diseases (eg, Turner syndrome, Klinefelter syndrome, hemochromatosis). Diagnosis of genetic disorders often indicates that relatives of the patient should be screened for genetic defects or carrier status.

Genetic screening

Genetic screening may be indicated in groups at risk for a specific genetic disease. Common genetic screening criteria:

  • known genetic patterns of inheritance;
  • effective therapy;
  • screening tests are sufficiently reliable, reliable, sensitive and specific, non-invasive and safe.

The prevalence in a given population must be high enough to justify the cost of screening.

One of the goals of prenatal genetic screening is to identify asymptomatic parental heterozygotes carrying the recessive disease gene. For example, Ashkenazi Jews are screened for Tay-Sachs disease, blacks are screened for sickle cell disease, and several ethnic groups are screened for thalassemia. If the partner of a heterozygote is also a heterozygote, the couple is at risk of having a sick child. If the risk is high enough, prenatal diagnosis (eg, with amniocentesis, chorionic villus sampling, umbilical cord blood sampling, maternal blood sampling, or fetal imaging) may be performed. In some cases, prenatally diagnosed genetic disorders can be treated, preventing complications from occurring. For example, special diets or replacement therapies can minimize or eliminate the effects of phenylketonuria, galactosemia, and hypothyroidism. Prenatal maternal use of corticosteroids may reduce the severity of congenital virilizing adrenal hypoplasia.

Screening may be appropriate for people with a family history of a dominantly inherited disease that appears later in life, such as Huntington's disease or cancers associated with disorders of the BRCA1 or BRCA2 genes. Screening clarifies a person's risk of developing the disease, who can therefore plan for more frequent screening or preventive therapy.

Screening may also be indicated when a family member has been diagnosed with a genetic disorder. A person who is identified as a carrier can make informed decisions about reproduction.

Treatment

Understanding the genetic and molecular basis of diseases can help guide therapy. For example, dietary restriction may eliminate toxic compounds in patients with certain genetic defects such as phenylketonuria or homocystinuria. Vitamins or other substances can alter biochemical pathways and thus reduce toxic levels of the compound, for example, folate (folic acid) reduces homocysteine ​​levels in people with methylenetetrahydrofolate reductase polymorphisms. Therapy may involve replacing deficient compounds or blocking the overactive pathway.

Pharmacogenomics. Pharmacogenomics is the science of how genetic characteristics influence response to drugs. One aspect of pharmacogenomics is how genes influence pharmacokinetics. A person's genetic characteristics can help predict response to treatment. For example, the metabolism of warfarin is partly determined by variants in the CYP2C9 enzyme genes, and for vitamin K protein complex 1 epoxide reductase. Genetic changes (such as in the production of UDP [uridine diphosphate] glucoronosyltransferase-lAl) also help predict whether the cancer drug irinotecan will have side effects.

Another aspect of pharmacogenomics is pharmacodynamics (how drugs interact with cell receptors). Genetic and thus receptor characteristics of damaged tissues can help establish clearer targets for drug development (eg, anticancer drugs). For example, trastuzumab can target specific cancer cell receptors in metastatic breast cancer that amplify the HER2I gene. The presence of the Philadelphia chromosome in patients with chronic myelocytic leukemia (CML) helps guide chemotherapy.

Gene therapy. Gene therapy can generally be considered any treatment that changes the function of a gene. However, chaao gene therapy is viewed specifically as introducing a normal gene into the cells of a person who lacks such normal genes due to a genetic disorder. Normal genes can be created using PCR from normal DNA donated by another person. Since most genetic disorders are recessive, the dominant normal gene is usually inserted. Currently, such gene insertion therapies are probably most effective for preventing or treating single-gene defects such as cystic fibrosis.

One way to transfer DNA into host cells is viral transfection. Normal DNA is incorporated into the virus, which then transfects host cells, thereby transferring the DNA into the cell nucleus. Some concerns about insertion using a virus include a reaction to the virus, rapid loss (failure to replicate) of new normal DNA, and damage to the defense against the virus by antibodies produced against the transfected protein, which the immune system recognizes as foreign. Another method of DNA transfer uses liposomes, which are taken up by host cells and thereby deliver their DNA into the cell nucleus. Potential problems with liposome insertion methods include the inability to absorb liposomes into cells, rapid degradation of new normal DNA, and rapid loss of DNA integration.

Gene expression can be altered using antisense technologies rather than inserting normal genes, for example drugs can combine with specific parts of DNA to prevent or reduce gene expression. Antisense technology is currently being tested for cancer therapy but is still in the experimental stage. However, it seems more promising than gene insertion therapy because the success rate of the insertion may be higher and there may be fewer complications.

Another approach to gene insertion therapy is to change gene expression chemically (for example, by changing DNA methylation). Such methods have been experimentally tested in the treatment of cancer. Chemical modification may also affect genomic imprinting, although this effect is unclear.

Experimentally, gene therapy is also being studied in transplant surgery. Changing the genes of the transplanted organs to make them more compatible with the recipient's genes makes rejection (and thus the need for immunosuppressive drugs) less likely. However, this process very rarely works.

Ethical debates in the field of genetics

There are concerns that genetic information could be misused to discriminate (for example, by denying health insurance or employment) against people with genetic risk factors for specific diseases. Issues include the privacy of a person's own genetic information and whether testing is mandatory

There is widespread support for prenatal screening for genetic disorders that cause serious disorders, but there is concern that screening may also be used to select for aesthetically desirable traits (eg, physical appearance, intelligence).

Cloning is highly controversial. Animal studies suggest that cloning is much more likely than natural methods to cause defects that are fatal or lead to serious health problems. Creating a human being through cloning is broadly unethical, generally illegal, and technically difficult.

EXPRESSIVENESS EXPRESSIVENESS

(from Latin expressio - expression), degree of phenotypic. manifestations of the same allele of a certain gene in different individuals. The term "E." introduced by N.V. Timofeev-Resovsky in 1927. In the absence of variability of a trait controlled by a given allele, they speak of constant E., otherwise - of variable (variable) E. Alleles decomp. genes can be characterized by different degree E., for example. alleles of the ABO blood group system in humans have practically constant E., and alleles that determine eye color have variable E. Classic. An example of variable E. is the manifestation of a recessive mutation that reduces the number of eye facets in Drosophila (in different flies homozygous for this mutation, a variable number of facets is observed, up to their complete absence). The phenomenon of variable E. is based on various factors. reasons: influence of external conditions. environment (see MODIFICATIONS) and genotypic. environment (under the same environmental conditions, an allele can manifest itself differently, depending on its combination with alleles of other genes). E. is one of the main. phenotypic indicators variability of gene expression, widely used in phenogenetics, honey. genetics, selection. The degree of E. is measured quantitatively using statistics. indicators. In cases of extremely variable E. (up to the absence of manifestation of the trait in certain individuals), an additional characteristic of the manifestation of genes is used - penetrance.

.(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.)


Synonyms:

See what “EXPRESSIVENESS” is in other dictionaries:

    See expressiveness Dictionary of synonyms of the Russian language. Practical guide. M.: Russian language. Z. E. Alexandrova. 2011. expressiveness of noun, number of synonyms: 13 ... Synonym dictionary

    - (in genetics) the degree of expression of a trait determined by a given gene. May vary depending on the genotype in which the gene is included and on environmental conditions... Big Encyclopedic Dictionary

    - [re], expressiveness, plural. no, female (book). distracted noun to expressive. Expressiveness of speech. Ushakov's explanatory dictionary. D.N. Ushakov. 1935 1940 … Ushakov's Explanatory Dictionary

    EXPRESSIVE, oh, oh; ven, vna (book). Containing expression, expressive. Expressive means of speech. Ozhegov's explanatory dictionary. S.I. Ozhegov, N.Yu. Shvedova. 1949 1992 … Ozhegov's Explanatory Dictionary

    EXPRESSIVENESS- (from Latin expressio expressiveness) of a gene, the degree of phenotypic manifestation of a gene. Ecological encyclopedic dictionary. Chisinau: Main editorial office of the Moldavian Soviet Encyclopedia. I.I. Dedu. 1989 ... Ecological dictionary

    EXPRESSIVENESS- (from Latin expresse expressively, clearly) in linguistics, the characteristic of linguistic units and speech acts as a means of expressing the subjective (personal) evaluative attitude of the speaker to the content or addressee of speech; E. is enhanced by paralinguistic... ... Great psychological encyclopedia

    expressiveness- - Topics of biotechnology EN expressivity ... Technical Translator's Guide

    Expressiveness- * expressivity * expressivity the degree of phenotypic manifestation of a particular gene (allele) as a measure of the strength of its action, determined statistically by the degree of development of the trait (see). E. gene in both sexes can be the same or different,... ... Genetics. encyclopedic Dictionary

    Expressiveness- (from Latin expressio expression) a set of semantic and stylistic features of a language unit that ensure its ability to act in a communicative act as a means of subjective expression of the speaker’s attitude to the content or... ... Linguistic encyclopedic dictionary

    EXPRESSIVENESS- The degree of stenotypic manifestation of a gene as a measure of the strength of its action, determined by the level of development of the trait. The expressivity of a gene in different individuals can be the same or different, constant or changing. Expressiveness is influenced by genes... ... Terms and definitions used in breeding, genetics and reproduction of farm animals

Books

  • Linguistic text analysis. Expressiveness. Textbook for bachelor's and master's degrees, V.A. Maslova. The book reveals the most important issues in the theory and practice of linguistic analysis of the expressiveness of a literary text. The authors propose an original concept of expressiveness based...

GENE EXPRESSIVENESS (Latin expressus explicit, expressive; gene; synonym gene expression) - the degree or measure of the phenotypic manifestation of a gene, that is, the degree and (or) nature of the expression of a hereditary trait among individuals of a certain genotype in which this trait is manifested. The expressivity of a gene is closely related to penetrance (see Penetrance of a gene), or manifestation, of a gene (see), as well as to its specificity. Together, penetrance and expressivity characterize the variability in the phenotypic expression of genes.

The concept of “gene expressivity” was introduced into the scientific literature by N. V. Timofeev-Resovsky and the German neurologist O. Vogt, who first used it in their joint work published in 1926. The need to introduce this concept was due to the fact that the term “genotype” unambiguously and uniformly defined the set of only those genes that control certain hereditary traits that do not change throughout an individual’s life (see Genotype). Such characteristics include, for example, blood type (see Blood Groups), antigens of erythrocytes and leukocytes of humans and animals (see Antigens), etc. However, more often it happens that the presence of a certain gene in the genotype is a necessary, but not sufficient condition for complete similarities between carriers of this gene according to the corresponding trait. In some individuals who are carriers of such a gene (in a homozygous state for recessive genes, and in a heterozygous state for dominant genes), it may not appear at all (so-called incomplete penetrance), and in some individuals in which this gene appears, its expression may be different, that is, the expressivity of this gene can vary (the so-called variable gene expressivity).

Variable gene expression is well known in medical genetics (see). Thus, complete Marfan syndrome (see Marfan syndrome) is characterized by arachnodactyly (see), joint laxity, the formation of aortic and pulmonary trunk aneurysms, subluxation or dislocation of the lens, kyphosis (see), scoliosis (see), etc. However, cases of manifestation in one patient, all wedges, signs characteristic of Marfan syndrome are rare. More often there are cases of “incomplete” Marfan syndrome, and even in one family the symptom complex is usually different for different family members.

The manifestation of polymorphic groups of similar traits, which is due to various genetic reasons, should be distinguished from the varying expressivity of one gene (see Genocopy). For example, in medical genetics a polymorphic group of forms (at least 7) ​​of Ehlers-Danlos syndrome is known, collectively characterized by different combinations, localization and severity of internal bleeding caused by ruptured blood vessels, increased skin extensibility, and joint laxity. A common pathogenetic factor in all these conditions is a violation of collagen biosynthesis (see). However, in different forms of the syndrome, disturbances are localized in different places in the biosynthetic chain of collagens. The genetic defects that cause them are also different: four forms of Ehlers-Danlos syndrome (see Desmogenesis imperfecta) are inherited in an autosomal dominant manner, two are inherited in an autosomal recessive manner, and one is inherited in an X-linked recessive pattern.

The reasons for varying gene expressivity may be interindividual genotypic differences (genotypic environment), variability in the expression of genes in individual development (see Ontogenesis) and the influence of environmental factors. For varying gene expressivity, all three reasons and the interaction between them are important.

The influence of the genotypic environment on both increased and decreased gene expressivity is proven by successful artificial selection: the selection of parental pairs with a better expressed hereditary trait automatically accumulates in the corresponding line modifier genes (see Gene) that favor the manifestation of this trait, and vice versa. In a number of cases, such modifier genes have been identified. The role of the genotypic environment in varying gene expressivity is also evidenced by the smaller range of intrafamily changes in the expression of hereditary traits compared to their interfamily variability. The influence of variability in the expression of genes in individual development on their expressiveness is illustrated by the incomplete concordance (or discordance) of genetically identical identical (monozygotic) twins (see Twin method) in terms of the degree and nature of expression of the same hereditary characteristics.

An example of the influence of environmental factors on gene expressivity is different coat pigmentation in animals of certain breeds depending on air temperature or improvement in the condition of patients with hereditary diseases (see) with appropriate pathogenetic treatment (for example, diet therapy, etc.).

Each of the three named reasons for varying gene expressivity in any particular case may have a greater or lesser share, but the general rule is that gene expressivity is determined by the interaction of genes and ontogenetic factors, as well as the influence of the environment on the organism as an integral system during ontogenesis. This idea of ​​gene expressivity is of great theoretical importance for understanding the mechanisms of ontogenesis of living organisms and the pathogenesis of hereditary human diseases. In medical genetics, this creates the basis for the search for pathogenetic methods for correcting hereditary defects, and in the selection and cultivation of agricultural plants and animals, it helps to create new varieties and breeds and their breeding in conditions that are optimal for better expression of economically valuable traits.

Bibliography: Bochkov N.P., Zakharov A.F. and Ivanov V.I. Medical genetics, M., 1984; Rokitsky P.F. Field of action of the gene, Zhurn. let's experiment biol., ser. A, t. 5, v. 3-4, p. 182, 1929; Timofeev-Resovsky N.V. On the phenotypic manifestation of the genotype, ibid., vol. 1, century. 3-4, p. 93, 1925; Timofeev-Resovsky N.V. and Ivanov V.I. Some issues of phenogenetics, in the book: Actual. question modern Genetics, ed. S. I. Alikhanyan, p. 114, M., 1966; Timofeef - Ressovsky N. u. Vogt O. Uber idiosomatische Variationsgruppen und ihre Bedeutung fur die Klassifikation der Krankheiten, Naturwissenschaften, Bd 14, S. 1188, 1926.