As a science, genetics arose at the turn of the 19th and 20th centuries. Many consider 1900 to be the official date of her birth, when Correns, Cermak and de Vries independently discovered certain patterns in the transmission of hereditary traits. The discovery of the laws of heredity took place, in essence, for the second time - back in 1865, the Czech natural scientist Gregor Mendel obtained the same results while experimenting with garden peas. After 1900, discoveries in the field of genetics followed one after another, studies on the structure of the cell, the functions of proteins, the structure of nucleic acids, discovered by Miescher in 1869, step by step brought a person closer to unraveling the mysteries of nature, new scientific directions were created, new methods were improved. And, finally, at the end of the 20th century, genetics came close to solving one of the fundamental issues biological science- the question of the complete decoding of hereditary information about a person.

220 scientists from different countries, including five Soviet biologists. Our country created its own program "Human Genome", headed by Academician Alexander Alexandrovich Baev.

The idea of ​​organizing such a program was first put forward in 1986. Then the idea seemed unacceptable: the human genome, that is, the totality of all its genes, contains about three billion nucleotides, and in the late 80s, the cost of determining one nucleotide was about 5 US dollars. In addition, the technologies of the 80s allowed one person to determine no more than 100,000 nucleotides per year. Nevertheless, already in 1988, the US Congress approved the creation of an American research project in this area, the head of the program, J. Watson, defined its prospects as follows: "I see an exceptional opportunity for improving humanity in the near future." The implementation of the Russian program began in 1989.

Now the determination of one nucleotide costs only one dollar, devices have been created that can sequence (from Latin sequi - follow) up to 35 million nucleotide sequences per year. One of the important achievements was the discovery of the so-called polymerase chain reaction, which makes it possible to obtain a DNA volume sufficient for genetic analysis from microscopic amounts of DNA in a few hours. According to experts, there is a possibility of completing the project in 15 years, and even now the program is producing useful results. The essence of the work is as follows: first, genome mapping is carried out (determining the position of the gene in the chromosome), localization of some genes, and then sequencing (determining the exact sequence of nucleotides in the DNA molecule). The first gene to be localized was the gene for color blindness, mapped on the sex chromosome in 1911. By 1990, the number of identified genes reached 5000, of which 1825 were mapped, 460 were sequenced. It was possible to localize the genes associated with the most severe hereditary diseases, such as Huntington's chorea, Alzheimer's disease, Duchenne muscular dystrophy, cystic fibrosis, etc.

Thus, the human genome research project is of great importance for the study molecular bases hereditary diseases, their diagnosis, prevention and treatment. It should be noted that over the past decades in industrialized countries, the share of hereditary diseases in the total volume of diseases has increased significantly. It is heredity that determines the predisposition to cancer and cardiovascular diseases. To a large extent, this is due to the ecological situation, with environmental pollution, since many industrial waste and Agriculture are mutagens, that is, they change the human gene pool. Given the current level of development of genetics, it can be assumed that scientific discoveries of the future will allow, by changing the genome, to adapt a person to adverse environmental conditions. As for the fight against hereditary diseases, their treatment by replacing diseased genes with healthy ones seems real now. All this means that a person will have the opportunity not only to change living organisms, but also to construct new forms of life. This raises a number of serious questions.

In my opinion, one of the most important issues is the question of the use of genetic information for commercial purposes. Despite the fact that both the participants of the HUGO project and representatives of international organizations, in particular UNESCO, are unanimous that any results of research on mapping and genome sequencing should be available to all countries and cannot serve as a source of profit, private capital is beginning to play an increasing role. role in genetic research. When the HUGO program appeared, so-called genomic companies arose, which took up their own work on deciphering the genome. Examples include an American organization called the Institute of Genomic Research (TIGR) or Human Genome Sciences Inc. (HGS). Between large firms there is a fierce struggle for patents. So in October 1994, Crack Venter, head of the aforementioned TIGR company, that his corporation had a library of 35,000 DNA fragments synthesized using RNA on laboratory-produced genes. These fragments were compared with 32 known genes for hereditary diseases. It turned out that 8 of them are completely identical, and 19 are homologous. TIGR turned out to be the owner of the most valuable scientific information, but its leaders have said that the chemical structure of all sequences in this library is classified and will only be made public if the company is recognized as the owner of all 35,000 fragments. This is not the only case, but meanwhile, the development of genetics is far ahead of the development of the corresponding legislative framework. Although steps are being taken in this direction (in Russia, for example, at the end of 1996 the law "On state regulation in the field of genetic engineering activities" was adopted, in 1995 a law on bioethics was adopted in France, in the USA the Civil Rights Act prohibits employment discrimination to work on racial, gender, religious and national grounds, while the gene for sickle cell anemia, in particular in blacks, can be considered a racial trait, another law prohibits discrimination in the employment of persons with reduced ability to work, and persons with a burdened heredity can also be considered as such , great importance has the so-called Tarasova principle, which obliges doctors to violate the confidentiality of medical information in order to prevent possible harm society), international acts regulating all aspects of activities related to genetics do not yet exist.

Medical genetics - a field dedicated to heredity, hereditary pathologies and health, treatment and prevention genetic diseases, as well as the problems of hereditary transmission of predisposition to diseases.

What is genetics?

An important part of medical genetics is clinical genetics, whose task is to detect and prevent hereditary pathology.

It is difficult to overestimate the role of genetics in modern medicine. As it turned out, it is huge, and even the considerable knowledge that has been accumulated in this area to date is, according to scientists, only the tip of the iceberg.

So, the doctors conducting it, it was found that many types of cancer are hereditary, in particular:

• leukemia;
• most oncological diseases of childhood;
• and etc.

New technologies, the gifts of scientific and technological progress, have opened up new opportunities for genetics, and from a predominantly theoretical discipline, it has become applied. The deciphering of the human genome has opened up the possibility of intervening in the genome, excluding some genes and activating others - this is the direction in which medical genetics is developing.

One of the important areas in which genetics is engaged is reproduction. Such a popular method of infertility treatment as IVF, which has become firmly established in medical practice, has also become possible thanks to the development of medical genetics. In addition, genetic diagnosis is always carried out when the patient has indications.

Methods of foreign genetics

There are the following methods of human genetics:

• Genealogical. The method consists in tracking and studying pedigrees, allows you to determine the patterns by which certain traits are inherited, including those that are responsible for hereditary diseases.
• Gemini. The method studies the influence of the environment on the human genotype by comparing identical twins living in different conditions.
• Cytogenetic. A method consisting in the microscopic examination of chromosomes. With its help, chromosomal diseases are determined (for example, one of the variants of Down syndrome).
• Sequestration. A method consisting in the study of human DNA at the molecular level.
• Dermatoglyphic. The method is based on the study of the relief of the skin of the fingers, palms and feet. With its help, a number of hereditary pathologies are diagnosed.
• Biochemical. It is used to study hereditary metabolic diseases, which are based on enzyme disorders.
• Population-statistical method – study of patterns of hereditary traits in large population groups.

Genetic diagnostics abroad

The genetics consultation includes genetic diagnostics. Genetic analysis allows you to determine not only the possibility of the appearance of hereditary diseases, but also predisposition to a number of common diseases.

For genetic analysis, blood is taken (5 ml), in addition, a thorough study of the patient's history is carried out - this is necessary in order to correctly interpret the results.

Most often, people turn to a genetic center or any other country if there are certain suspicions of a possible hereditary pathology, if one of the family members (including a born child) has such a pathology, and during pregnancy, if there are certain indications.

Genetic diagnostics in pregnant women, with reasonable suspicions of the possibility of a hereditary pathology, is also carried out by invasive methods:

Treatment of genetic diseases abroad

Genetics abroad, thanks to the availability of cutting-edge equipment and trained specialists, has great potential in the diagnosis of all types of hereditary pathology. Patients turn to the Department of Genetics as directed by a doctor if there are certain indications (for example, families planning a child, if there is a confirmed genetic pathology in already born children) or at their own request.

Regardless of whether it is a major institute of genetics, a center of genetics or a department of genetics, the patient will receive qualified assistance in full.

Each IVF medical diagnostic center also has the possibility of genetic diagnostics according to modern standards - that is why among children born through artificial insemination, there are practically no those who would suffer from hereditary diseases.

The cost of treatment in genetics centers abroad

If you need advice on genetics, the UNIMED website offers you to fill out a contact form and contact us. We will provide you with comprehensive information, including the possible cost of genetic diagnosis and treatment. Also on this portal you can find out official and other countries.

Human genetics is a science that combines genetics and medicine. It is devoted to the patterns of inheritance, change, human evolution. The genetics of...

By Masterweb

03.04.2018 20:00

Human genetics is a science that combines genetics and medicine. It is devoted to the patterns of inheritance, change, human evolution. This science considers both individuals whose condition is fully consistent with the norm, and those who have various individual signs of physiology, psychology inherited from birth, as well as pathological conditions. Genetics also considers behavioral aspects. The main task of scientists is to determine what is formed under the influence of the environment, and what is a manifestation of the genotype.

General view

Human genetics is based on general patterns- these are universal, they can be applied to a variety of species and individuals, and man is no exception. Currently, more than 3,000 signs inherent in humans have been identified. They affect morphology, biochemistry, physiology. 120 of them are related to gender. Scientists were able to identify and study 23 types of genetic linkage. It was possible to make a map of chromosomes, on which many genes are fixed.

Particularly noteworthy are studies conducted as part of the refinement of human genetics, devoted to small populations, that is, to such societies in which there are no more than one and a half thousand people. Scientists have found that for such a group of people, the frequency of marriages inside exceeds 90%, therefore, in just one century, all participants become second cousins ​​to each other. Studies have shown that under such conditions, the risk of recessive mutations increases. About eight percent of them are lethal, some are associated with the structure of the eyes or the skeleton. Mutations are often observed already at the stage of fetal formation, which leads to its premature death - even before birth or immediately after birth.

Features and figures

Investigating human genetics, it was possible to reveal that the haploid set is a combination of genes in an amount of at least 100,000, but in some this number reaches a million. One genome is a source of mutations from one to ten. An increase in the probability of mutations by 0.001% for a particular individual means practically nothing, but when assessing the health of the population, the picture changes - the number of patients is measured in hundreds and thousands. By analyzing the information received, scientists were able to assess how important the mutagenic influence of the world around us is. It is by examining it on a population scale that one can realize the magnitude of the problem.

Studying the human genome in genetics, it was possible to establish that a person has some specific features, due to which scientific progress slows down. In particular, the karyotype has a huge number of chromosomes, in addition, few children are usually born in marriage. And during pregnancy, mostly a woman bears only one child. Exceptions are possible, but rare. The complexity of the study of human genetics is associated with the duration of maturation and the slow change of generations, as well as the inability to form a marriage base, organize experimental crossing, and use artificial technologies to activate mutations.

The study of human genetics is not only a forced struggle with difficulties and problems, but also a number of specific advantages. Mutations are characteristic of humans, and their diversity is only growing at the present time. In addition, the physiology and anatomy of the species have been studied in detail. The population as a whole is numerous, which means that scientists can choose among the existing marriage schemes that best meet the goals of the ongoing scientific work.

Don't stand still

The tasks of human genetics are to study how inheritance occurs, in what forms genetic traits appear in different individuals. Currently, scientists know for sure that from person to person, the set of features changes quite significantly. This is explained by the relevance of all types of inheritance: by dominant, recessive gene, autosomal, codominant, in linkage with the sex chromosome. To achieve maximum accuracy of research, it is necessary to use specific methods - those designed specifically for studying a person. Work continues on new methods and methods that will provide more information on this topic.

For more than a decade, scientists have not only collected new information. In human genetics, analytical approaches are used that involve the analysis of already known data, taking into account new information received. Such an ongoing analytical process allows expanding the catalog of human traits that are transmitted between generations.

Man and science

The study of human genetics involves the study of the mechanisms of inheritance and the characteristics of the variability inherent in man as a species. An alternative term for science is anthropogenetics. Science is devoted to the differences and commonalities of people, explained by the hereditary factor. It is now customary to classify medical genetics as a separate category. This area is devoted to inherited diseases, methods of their treatment and prevention. The relevance of research is closely related to the large accumulated information base on this issue. It was possible to obtain fairly clear information about the morphology and physiology, biochemistry of man. All this information is relevant in the study of the genetic specificity of the representatives of the population.

Features of the study of heredity, human genetics is a science closely related to the characteristics of society, ethics, and human biology. At the same time, it is taken into account that a person has the ability to think abstractly, to perceive data. These features are considered undeniable advantages that are not inherent in other objects studied by genetics.

Research: how are they organized?

In human genetics, methods are used: cytogenetics, statistics, population research, ontogenetics, genealogy, modeling. The twin approach to the study of man is widespread. Interesting and giving a lot useful information way - dermatoglyphics. In human genetics, the hybridization method is used, using somatic cells as a material for work. Approaches that allow working at the molecular level are also relevant.

In addition to the main ones, auxiliary methods are used - they are designed to obtain additional information. Those involve the use of methods of microbiology, biochemistry, immunology and other related disciplines.

Genealogy

This method of human genetics is based on the study of traits, properties that are inherited from person to person. To study, it is necessary to have access to the pedigree of the individual. For the first time such an approach was developed by Galton, and to simplify its application, Yust subsequently proposed the use of conditional symbolism. Genealogy involves the formation of a pedigree and subsequent analysis of information.

Within the framework of this method of human genetics, it is first necessary to collect comprehensive data on the family. Further, the information is recorded graphically, using standard symbols. As part of the analytical study of the collected database, it is assessed whether a particular trait can be called a family trait, and also determine by what mechanism it is transmitted. Scientists investigate what the genotypes of close relatives are, calculate the risks of the appearance of the analyzed trait in future generations. For different inheritance mechanisms are characteristic individual characteristics, and their features are visible in the analysis of the pedigree.

About details

For analytical work in this method of studying human genetics, it is first necessary to form an idea of ​​the rules for the monogenic transmission of properties by inheritance. Mendelian signs, studied in this way, are discrete, determined, split. To assess discreteness, it is necessary to analyze morphology, physiology, biochemistry, immunology, and clinical criteria.

Particularly detailed information on the systematization of traits can be found in the works of Cusick, who published a catalog of Mendelian human traits. Genealogy as a method of research is comparable to the hybridological method, and the differences are explained by social characteristics and human biology. Currently, this approach is widely used in studies of mutations, sex-linked inheritance, as well as in the framework of medical genetic counseling.

twin way

This method of studying human genetics involves the presence of pairs of twins. Objects are investigated, scientists identify what are the similarities between them, what are the differences. Twins are considered only those children who were born and at the same time were born to one mother. There are mono- and dizygotic forms. In the first case, the source material is one zygote, while the genotypes are the same, the sex is the same. With two zygotes, the genotypes of the twins are different, and the sex may or may not be the same.

When the twin method is used to study human genetics, zygosity is first detected by a polysymptomatic approach. People are assessed for similarity on the grounds for which inheritance is established, and the influence of the environment on them is minimal. When it is possible to determine exactly the zygosity, individuals are compared according to a specific trait.

A concordant pair is detected if some feature is present in both twins. In its absence, one of the twins speaks of a discordant pair. If the twin method is used to study human genetics, it is taken into account that the information obtained most accurately allows one to assess the role of inheritance, how much the environment influences the correction of a particular trait. Scientists can determine which traits are inherited, why genes differ in penetrance. As part of the study, it is possible to assess how effectively external factors influence an individual - from medication to approaches to education.

Cytogenetics

Human medical genetics involves the study of cellular structures under a microscope. In this study, attention is paid to chromosomes. The main task of a specialist is to identify sex chromatin, to conduct karyotyping. This process is necessary to identify metaphase chromosomes.

A karyotype is a diploid chromosome set characteristic of a particular species. An idiogram is a karyotype fixed in the form of a diagram. Karyotyping is effective if there are individual lymphocytes. First, a certain number of cells capable of dividing are removed, metaphase plates, a hypotonic solution are obtained. Systematization is carried out by one of two methods - Parisian or Denver.

The Denver variant involves taking into account the shape and size of the chromosome, and the method of continuous staining is used in the work. There are seven categories of chromosomes. The difficulty of applying the approach is that it is not easy to identify individual chromosomes within a group.

The Paris method of classification involves staining of metaphase chromosomes. Each of them has a unique pattern, and the discs allow for clear differentiation.

Prenatal diagnosis

Genetics and human health are closely linked. To prevent the birth of a child suffering from pathological abnormalities, prenatal diagnosis is used. This measure is considered the primary way to prevent diseases that are inherited. Several approaches to diagnosis are known, the choice in favor of a particular one depends on the specifics of the family and the condition of the expectant mother.

An indirect method for studying human genetics with the basics of medical genetics involves the study of pregnant women to determine risk groups. The blood is checked for alpha-fetoprotein, the parameters of hCG, estriol are revealed. It is known, for example, that Down's disease is often observed with elevated hCG and low estriol. From the indicators of alpha-fetoprotein, one can conclude how high the probability of pathologies of the neural tube, skin, and the risks of chromosomal diseases.

Alternative option

Within the framework of the fundamentals of human genetics, direct approaches to prenatal diagnosis have been developed. These are invasive and non-surgical. Non-invasive - the study of the condition of the fetus using ultrasound. So you can determine multiple pregnancy, some diseases and defects.

Direct invasive methods include chorionbiopsy, placentobiopsy, amniocentesis, cordocentesis, fetoscopy. To study the condition, samples of the skin of the fetus can be taken. Materials and samples obtained for subsequent work are studied through the approaches of cytogenetics, biochemistry, molecular composition and genetic features are checked. The findings are used when advising future parents on issues of heredity. Human genetics at the stage of prenatal diagnosis reveals the risk of chromosomal diseases and molecular abnormalities. In addition, it is these methods that are used to determine the sex of the unborn child and assess the likelihood of fetal malformations.

Modeling and genetics

If the genealogical method of studying human genetics allows us to estimate the probability of inheriting traits based on their observation in previous generations, then modeling is an approach in which hereditary variability is used to form an object model. Vavilov's laws are applied, indicating that genetically close species, genera have similar series of variability, which is inherited. Phylogenetically close individuals give an unambiguous response to external factors, including provoking mutations.

By resorting to mutant lines characteristic of animals, it is possible to form models of the inheritance of a number of diseases characteristic of both animals and humans. Scientists receive new methods of studying the ways of formation of diseases, methods of their transmission by inheritance. Currently, there are new approaches to diagnosis, based on the achievements of genetics. The data obtained from the study of animals are applied to humans after certain amendments have been made.

Biochemistry and statistics

The ontogenetic method, relevant to the study of human genetics, involves studying using biochemical approaches to identify metabolic problems and failures, individual for a particular object, if any are explained by a mutation. In the body of an object, intermediate products of metabolic reactions can be observed, and their detection in organic fluids has been widely used in approaches to the diagnosis of pathological conditions.

Population statistics and research is an approach in modern genetics that involves the study of the genetic composition of populations. Having collected a sufficiently voluminous database, one can estimate how high the chance of an individual with a given phenotype appearing in the group of people under study. You can calculate the frequency of gene alleles, genotypes.

Another approach applicable today is molecular genetics. This is the same genetic engineering that many have heard of, although not every person can imagine what the essence of the work of scientists is. Engineering consists in isolating genes and creating their clones, forming recombinant molecules and placing them in a living cell. Templates obtained during the synthesis of new nucleic acid chains are used for replication. Molecular genetics actively uses the sequencing approach and some other high-tech methods.

Genetics and human characteristics

Heredity is provided by the presence of genes, whose carriers are chromosomes. The object receives a set of genes from the mother, father. Between generations, transmission is realized through germ cells. In the body, the gene is presented twice, transmitted by mother and father. Genes can be identical, they can differ. In the first case, they speak of homozygosity, in the second - heterozygosity. The probability of the first option is extremely low, because there are too many genes. If there is a common line of ancestors, the chance of homozygosity is higher, since the father and mother pass on identical genes to the child. In practice, this is not common due to the institution of marital relations and existing laws. The philological foundation of the uniqueness of the personality, its originality is explained by the diversity of the genetic set in each case.

Population human genetics is one of the most important branches of science. The human population differs significantly from other species, as it is a product of history, natural selection, and the development of society. Genetic reproduction is both a biological process and a social one, connected with demography and inseparable from it and population reproduction. The transfer of data between generations and the distribution of genetic sets, migrations and mutual connections with the environment surrounding a person ensure the movement of genetic material. It is safe to say that genetics and demography are closely related aspects; population genetics is actually demographic, and scientists who study it study the results of processes inherent in demography.

Nuances and features

A long study of genetics and demographic changes allows us to conclude with confidence that the gene pool is constant over time, although it is represented in each particular generation by an abundance of unique genotypes. Constancy is ensured by fertility and mortality, the movement of carriers of genetic information. The population gene pool can change, since different carriers of the material are involved in the process of reproduction with varying degrees of activity. This feature is an element of natural selection, under the influence of which the structure of the gene pool changes, and the community is more consistent with the conditions of the environment in which a person lives.

In the human population, the change in the gene pool is to some extent due to mutations, genetic drift and migration. Natural mutations are a process whose rate is considered to correspond to a normal change in the gene pool. The genotypes formed in such a process may be completely new, previously uncharacteristic of the community. Regular gene migration smooths out the differences between populations, leads to the loss of originality, uniqueness, due to the local specifics of the environment.

Gene migration is due to the migration of carriers of genetic material. Currently, there is no way to unambiguously assess and describe the role of migration in human development. A number of consequences of migration are obvious, the main percentage of the world's population is the product of a mixed population.

stability and progress

The chance that there will be no mutations, migrations, genetic selection is extremely small, but even if we imagine that this is possible, the possibility of changing the gene pool still remains. This is due to genetic drift, that is, the process of genetic adjustment at the population level. In particular, a small population can lead to drift. As a rule, drift is characteristic of endogamous societies, whose distinguishing feature is a small number of genotype carriers, while the potential diversity of sets of traits is exceptionally high.

The small size of the population allows only a small percentage of possible sets of features to be realized in each new generation. Consequently, the gene pool of each new generation appears as a product of a random selection of a certain number of genes transmitted from parents.

Within the framework of demographic genetics, genetic drift is considered to be an environmentally independent process. Exploring small human populations, one can notice how the level of development of culture, society, and the economy affects the population, how this affects the nature of interaction with the environment. Genetic drift, determined by the number of people in society, depends on the specifics of society and the environment in which it exists.

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Introduction to genomics. The human genome, the main features of the organization. Methods for studying the human genome

The value of the human genome study program for practical medicine.

The 21st century is the era of genomics - the time when the DNA sequence in the human genome is almost completely determined, the time when the role of thousands of human genes in health and disease is analyzed. The time of personalized medicine is coming - when the study of small variations in many genes will lead to the identification of a person's individual predisposition to a particular pathology.

The most important events in genetics of the 20th century, initiating the study of the genome:

Discovery of the DNA double helix (J. Watson, Fr. Crick, 1953)

Development of DNA sequencing method - 1997

Isolation of human embryonic stem cells (1998)

A decisive achievement in molecular biology was the development of DNA sequencing methods in 1977.

The International Human Genome Project officially started in 1990. A huge contribution was made by scientists from 6 countries - the USA, Great Britain, France, Germany, Japan and China. By 2001, 90% had been sequenced with 99.99% accuracy. By 2003, 99% of the human genome had been sequenced. There are about 400 gaps left.

During the implementation of the Human Genome Project, the DNA sequence of all chromosomes and mitochondrial DNA was determined.

The twenty-two autosomal chromosomes, the two sex chromosomes X and Y, and human mitochondrial DNA together contain approximately 3.1 billion base pairs.

Full sequencing revealed that the human genome contains 20-25 thousand active genes, which is significantly less than expected at the beginning of the project (about 100 thousand) - that is, only 1.5% of all genetic material codes for proteins. The remainder (97%) is non-coding DNA, often referred to as junk DNA. The human genome is the totality of hereditary material contained in a human cell.

In general, the word "genome" refers to the total amount of DNA in a given species, including not only genes, but all other DNA. In humans, for example, protein-coding sequences account for only 1.25% of the entire genome. What is the human genome?

The share of introns is up to 20-25%. But a significant part of intergenic DNA is occupied by regulatory sequences.

Gene classifications:

Genes active and repressed

The bulk of the genes that are actively functioning in most body cells throughout ontogenesis are genes that provide the synthesis of general-purpose proteins (ribosomal proteins, histones, tubulins, etc.), tRNA and rRNA. Such genes are called constitutive. The work of another group of genes that control the synthesis of specific proteins depends on various regulatory factors. They are called regulated genes. Changing conditions can lead to the activation of "silent" genes and the repression of active ones. Differential expression of the genome in mammals determines the development of a huge variety of tissue types.

Coding proteins and RNA

Protein coding sequences (the many sequences that make up exons) make up less than 1.5% of the genome.

In addition to protein-coding genes, the human genome contains thousands of RNA genes, including transfer RNA (tRNA), ribosomal RNA, microRNA (microRNA), and other non-protein-coding RNA sequences.

Structural genes characterized by unique nucleotide sequences encoding their protein products, which can be identified by mutations that disrupt the function of the protein.

Housekeeping genes and luxury genes.

All genes are divided into "housekeeping" genes and "luxury" genes.

The "housekeeping" genes encode what any cell always needs, regardless of the tissue. Housekeeping genes are genes necessary for maintaining the body's essential life functions and are expressed in virtually all tissues and cells at a relatively constant level. Housekeeping genes function everywhere, at all stages life cycle organism.

According to various estimates, there are 10-20 thousand such genes in humans. These are histone genes, tRNA genes, rRNA genes, etc.

The "luxury" genes, which are obviously 2-3 times more numerous, are genes that are expressed in the cells of certain tissues and at a certain time. For example, all genes for protein hormones are "luxury" genes.

Regulatory sequences are nucleotide sequences that do not code for specific proteins, but regulate the action of a gene (inhibition, increase in activity, etc.).

Many different sequences have been found in the human genome that are responsible for gene regulation. Regulation refers to the control of gene expression (the process of building messenger RNA along a section of a DNA molecule). These are usually short sequences that are either adjacent to the gene or within the gene. Sometimes they are at a considerable distance from the gene (enhancers).

Silencer is a DNA sequence to which repressor proteins (transcription factors) bind. Binding of repressor proteins to silencers leads to a decrease or complete suppression of RNA synthesis.

Insulators

The human genome consists of 23 pairs of chromosomes located in the nucleus, as well as mitochondrial DNA in the form of 2-6 circular molecules. human chromosomes. Chromosome size varies from 45 million to 280 million bp.

The chromosome is not homogeneous. It alternates between areas of euchromatin (not dense areas) and heterochromatin (more dense). With differential staining along the length of the chromosome, a number of stained (heterochromatin) and unstained (euchromatin) bands are revealed. The nature of the transverse striation obtained in this way makes it possible to identify each chromosome in the set, since the alternation of the bands and their sizes are strictly individual and constant for each pair.

EUCHROMATIN, a substance of the chromosome that maintains a despiralized (diffuse) state in the resting nucleus and spiralizes during cell division. Contains most of the structural genes of the body. Heterochromatin - extended sections of repetitive and highly condensed sequences that do not encode any proteins.

Classification of heterochromatin:

Optional (Depending on the stages of the cell cycle, cell type, the same part of the chromosome can be in the state of both hetero- and euchromatin. Such parts of the chromosomes are called facultative heterochromatin.

Constitutive (pericentromeric, telomeric) Areas that are always compacted. These sections of chromosomes contain tandemly repetitive DNA (arranged one after the other "head to tail").

Pericentromeric heterochromatin consists of short tandem repeats up to 20 bp long, organized into long blocks (100–200 tandems each). Blocks form rows from 250 thousand to 5 million bp in length. This type of DNA is called satellite, alpha (alpha-satellite). They make up 3% of the genome. In the locations of satellite DNA, maximum compaction is possible; all four levels of DNA packaging are present even in interphase. On satellite DNA, crossing over occurs between homologous chromosomes.

Telomemra (from other Greek felpt - end and mEspt - part) - minisatellites - end sections of chromosomes. In most eukaryotes, telomeres consist of short tandem repeats and contain thousands of 6-nucleotide repeats: in humans - TTAGGG (for comparison, in all insects - TTAGG, in plants - TTTAGGG). They are repeated from 250 to 1500 times.

Several proteins are associated with telomeres, forming a protective "cap" - a telomere complex that protects telomeres from the action of nucleases and adhesion, and, apparently, it is this that maintains the integrity of the chromosome and protects the entire chromosome from destruction. Telomeric regions of chromosomes are characterized by a lack of ability to connect with other chromosomes or their fragments and perform a protective function.

With each cycle of division, cell telomeres shorten due to the inability of DNA polymerase to synthesize a copy of the DNA from the very end. DNA polymerase can only start chain synthesis from an RNA primer. After DNA synthesis is completed, the RNA primers on the lagging strand are removed, and the gaps are filled in by DNA polymerase. However, at the end of the chain, such a gap cannot be filled. Therefore, 3" DNA segments remain single-stranded, and 5" underreplicated. Therefore, EVERY ROUND OF REPLICATION WILL REDUCE THE END OF THE CHROMOSOME. This phenomenon is called terminal underreplication and is one of the most important factors of biological aging. So, in a newborn, the length of telomeres varies about 15 thousand bp; in chronic diseases, it decreases to 5 kb. Scientists from Cardiff University have found that the critical length of the human telomere, at which chromosomes begin to connect with each other, is 12-13 telomeric repeats.

With such a critical shortening of telomeres, the structure of chromosomes is disrupted, adjacent genes can be damaged, and chromosomal aberrations begin to form, which often lead to malignancy. To prevent this from happening, special molecular mechanisms block cell division, and the cell goes into a state of rest - an irreversible stop of the cell cycle. As a result, the cell may die or stop dividing. It occurs in most normal somatic cells, which have a limited ability to reproduce. Many stimuli can bring the cell into a state of such rest - telomere dysfunction, DNA damage, which can be caused by mutagenic environmental influences, endogenous processes, strong mitogenic signals (overexpression of oncogenes Ras, Raf, Mek, Mos, E2F-1, etc.) , chromatin disorders, stress, etc.

However, in germ, germ and stem cells there is a special enzyme - telomerase, capable of restoring telomeric sequences that are shortened with each replication event.

Protective mechanisms of terminal underreplication.

There is a special enzyme - telomerase (RNA + protein), which, using its own RNA template, completes telomeric repeats and lengthens telomeres. In most differentiated cells, telomerase is blocked, but is active in stem and germ cells.

Telomerase reactivation is believed to be an important step in malignant processes, as it allows cancer cells to “overlook” the proliferation limit. Telomere dysfunction contributes to chromosomal fusions and aberrations, which most often leads to malignant neoplasms. Active telomerase is found in 90% of cancerous tumors, which ensures the uncontrollable reproduction of cancer cells. Therefore, at present, among the drugs that are used to treat cancer, there is also a telomerase inhibitor.

For the discovery of protective mechanisms of chromosomes from terminal underreplication using telomeres and telomerase in 2009 awarded Nobel Prize in Physiology and Medicine, an Australian working in the USA, Elizabeth Blackburn (Elizabeth Blackburn), American Carol Greider (Carol Greider) and her compatriot Jack Szostack (Jack Szostack).

Besides, in last years telomeric DNA has become the subject of intense study due to the discovery of a link between telomere shortening and aging.

Other classes of tandem repeats are genes for RNA, such as ribosomal. These genes are located in the NOR of 5 pairs of acrocentric chromosomes.

Another group of repeats are dispersed repeat sequences that are scattered throughout the genome individually rather than in tandem. They are mobile (mobile) genetic elements - retrotransposons. 15% of the genome is occupied by long dispersed elements - LINE, 12% - short SINE. These sequences produce enzymes - endonucleases, capable of making cuts in DNA and inserting their sequences there. Insertion of MGE into DNA can disrupt the function of the gene. In humans, about 30 retrotranspositions are known to cause disease. Why does the genome not get rid of such dangerous areas? Repeat sequences and MGEs are an important source of genome remodeling.

The systematization of these sequences, understanding of the mechanisms of work, as well as the issues of mutual regulation of a group of genes by a group of corresponding enzymes are currently only at the initial stage of study. Mutual regulation of groups of genes is described using networks of gene regulation. The study of these issues is at the intersection of several disciplines: applied mathematics, high-performance computing and molecular biology. Knowledge emerges from comparisons of genomes various organisms and thanks to advances in the field of organizing artificial transcription of the gene in the laboratory.

All genes are divided into structural and functional genes according to their functions.

Structural genes carry information about the structure of proteins and RNA.

Functional genes include:

modulator genes that enhance or weaken the work of structural genes (suppressors (inhibitors), activators, modifiers);

genes that regulate the work of structural genes (regulators and operators).

genome underreplication protein

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Created 4 years ago with the aim of deciphering the information encoded in the human genome as completely as possible, they announced the completion of the first stage of work. More than 300 researchers from the US and other countries have conducted a detailed analysis of the structure and function of one hundredth of the human genome (30 million base pairs out of 3 billion). An unexpectedly large variety of transcripts, RNA molecules synthesized on a genomic DNA template, have been found in human cells. It turned out that 80% of the genome undergoes primary reading (transcription), despite the fact that only 2% of the genome encodes proteins. This and other results suggest that the mechanisms of the functioning of the genome are more complex than is commonly believed, and the “language” in which hereditary information is recorded is not yet fully understood by us.

Although the human genome was declared “roughly read” back in 2000-2001, and in 2003-2004. talk about "almost complete reading", science is still far from a complete understanding of the information encoded in the genome. To solve this global problem in 2003, the National Human Genome Research Institute (NHGRI) launched the ENCODE project ( Enc yclopedia o f D NA E lements), bringing together hundreds of scientists and dozens of research teams from the United States and other countries.

The maximum task facing the project participants is to find out why it is needed and what encodes each of the 3 billion nucleotides of the human genome. And to find out not only theoretically, in silico(by computer analysis of DNA sequences), but also to confirm the results experimentally. The solution to this problem, of course, is still very far away. In the meantime, scientists reported on the completion of the first stage of work, the purpose of which was mainly to develop methods and test strength.

Scientists used the entire vast arsenal of tools and methods of modern genetics, genomics and molecular biology. In particular, the comparison of the human genome with the genomes of other mammals was widely used (see: The genome of the rhesus monkey will tell about human evolution, "Elements", 04/19/2007; Reading the possum genome proved the key role of transposons in the evolution of mammals, "Elements", 05/13/2007 ). Such a comparison allows us to identify "conservative", that is, similar in different types sections of the genome. Conservatism usually indicates the functional importance of this area (see: Comparison of human and mouse genomes helped to discover a new way of regulating the work of genes, "Elements", 04/21/2007).

But the main "horse" of the ENCODE project is a total analysis transcriptome, that is, those RNA molecules that are synthesized by the cell on the genomic DNA template during transcription - "reading" of genetic information. Recall that the information encoded in classical protein-coding genes is realized in two stages: first, RNA is synthesized on the DNA template (transcription), then protein is synthesized on the RNA template (translation).

It was previously known that only 2% of the human genome encodes proteins. Only these two percent of the genetic "text" undergo not only transcription, but also translation. It was also known that many untranslated regions of the genome are also subjected to transcription. These are, firstly, functional RNA genes (transport, ribosomal and various regulatory ones), and secondly, introns, non-coding "inserts" found in most protein-coding genes. Before translation, introns are cut out of RNA molecules (this is called splicing). One of the main achievements of the ENCODE project is that it was finally possible to find out what proportion of genomic DNA undergoes transcription in human cells. It turned out - as much as 80%, much more than expected. Prior to the start of the project, it was known that in the hundredth part of the genome that was to be studied, there were 8 non-translated RNA genes. It turned out that in reality there are thousands of them.

Researchers cannot yet say exactly what function all these transcripts perform. It is possible that some of them do not perform any special function and are just a by-product of the activity of RNA polymerase enzymes - an activity that is probably somewhat chaotic (on the chaotic aspects of the work of some proteins, see: The work of a regulatory protein was first observed under a microscope , "Elements", 05/31/2007; The mechanism of movement of the "walking squirrel" has been unraveled, "Elements", 05/29/2007). But many of the discovered transcripts are still needed for some reason. This is confirmed by the fact that they contain conserved regions that are almost identical in humans and mice.

The study of transcripts read from ordinary protein-coding genes also brought surprises. In total, there are 400 such genes within the studied region of the genome. In more than 80% of them, transcript analysis revealed the presence of previously unknown functional fragments - exons (exons, unlike introns, are those parts of the gene that encode a protein). Some of these exons have been found to be thousands of base pairs away from all other exons in the same gene in genomic DNA, sometimes even within another gene. The fact that the genes of higher organisms consist of coding pieces-exons, separated by non-coding inserts-introns, has long been known, but no one knew that the exons of many human genes are so far apart and so bizarrely scattered. Moreover, transcripts containing exons of two different genes were found.

All this makes us admit that we still do not have a very good idea of ​​what a gene is and how it works. Some of the project participants even allowed themselves to speak in the press in the sense that, they say, the gene is a somewhat outdated concept, but in fact the fundamental units of the genome are transcripts (as one of the theorists said, “we still live in a world of RNA"). Others do not agree with this: in their opinion, the gene remains the central object of molecular biology, but the definition of this concept needs to be corrected.

In the course of the project, the researchers developed a number of new techniques that will be useful to them in the future - for example, they learned much better to search for regulatory regions of DNA, including transcription start sites (promoters) - nucleotide sequences that signal RNA polymerases that this place to start transcription. Before the start of the ENCODE project, 532 promoters were known in this part of the human genome, now there are already 775 of them, and in addition there are many hypothetical ones awaiting experimental confirmation.

Let's name some of the obtained results:

Histones - special proteins on which genomic DNA is "wound" in the cell nucleus - are modified in a certain way near the transcription start sites and other regulatory elements; the nature of these modifications can even predict the presence of certain regulatory elements in a given DNA region.

Approximately 5% of the nucleotides in the mammalian genome are certainly under the influence of stabilizing (purifying) selection, in other words, they are conservative - the rate of their evolutionary changes is greatly slowed down.

For 60% of these conservative bases, there is experimental confirmation of the presence of a function - that is, they are really needed for some reason, they encode something.

Many DNA fragments with an experimentally confirmed functional role are not, however, evolutionarily conserved - the nucleotide sequence in them changed rapidly during the evolution of mammals. Apparently, many of these regions encode functions that are not vital. Such sites can serve as good "material for selection". By the way, the researchers themselves consider this result to be the most unexpected: they used to think that almost everything functional in the genome should be conservative.

Functional DNA fragments have varying degrees of variability within the human population: some of them are almost the same in all people, others can vary greatly.

The cost of the first stage of research was $42 million. NHGRI intends to allocate $23 million annually to continue the work. It is assumed that in 4 years the entire human genome will be subjected to the same in-depth analysis as the hundredth part studied to date. Speeding up and reducing the cost of the process will be ensured by new methods developed by the project participants.

Sources:
1) The ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project (full text — Pdf, 4.5 Mb) // Nature. 2007. V. 447. P. 799-816.
2) Elizabeth Pennisi. DNA Study Forces Rethink of What It Means to Be a Gene // Science. 2007. V. 316. P. 1556-1557.

For human genome research, see also:
1) The Human Genome Project.
2) Human evolution was accompanied by a change in the activity of regulatory genes, "Elements", 03/13/2006.
3) People differ from chimpanzees not in what they wanted, "Elements", 11/30/2006.
4) Will the genetic foundations of the mind be deciphered? , "Elements", 09.10.2006.
5) Why chimpanzees don't get cancer, Elements, 02/08/2006.