Hereditary diseases: it is possible to identify now, to cure – not yet soon
Software-controlled molecular bombsViola Brick, "Around the World"
When they talk about "bad" or "good" genes, they usually mean the obvious qualities of a person. But many genes do not manifest themselves in any way. We will find out about their existence at the most inopportune moment. They are beneficial to evolution, but remain a puzzle for medicine.
The race for the genomeThe human body is formed and develops far from randomly.
All the processes taking place in it obey a certain plan, written in a rather complex language – in the form of a linear sequence of base pairs of a DNA molecule. Fifteen years ago, this language was a mystery to science. In 1990, the interstate program "Human Genome" (Human Genome Project) was launched in the USA. The project involved the state laboratories of eighteen countries of the world, and they managed to almost completely decode the human genome by 2003. Interestingly, similar studies were conducted by the private company Celera genomics, whose management plans included obtaining a patent for each open gene and, as a result, making a profit for providing information. Competing organizations, by mutual agreement, simultaneously announced the completion of the work. On June 26, 2000, it was announced that the human genome was 97% decoded. Today, research has moved into a different field: from structural genomics to functional genomics, which will help to establish how genes are controlled and work.
Most of the human genome is concentrated in the DNA of cell nuclei. This genetic material is organized into a paired set of chromosomes. A person receives half of the chromosomes from his mother, the other half from his father. At the same time, each external feature, be it hair color or skin tone, is determined by two genes (one from each parent). Depending on which gene dominates, the child becomes somewhat similar to either the father or the mother. It turns out that in order to transmit important traits, genes must be reliably protected. Indeed, a healthy genome is constantly "checked" by special enzymes that identify and fix problems. But such a mechanism is not always effective, so from time to time mutations occur in the genome – modifications of a particular site in the structure of the gene, for example, its lengthening, shortening, changing the meaning. Mutations can occur either spontaneously or under aggressive influences, such as ultraviolet radiation. From an evolutionary point of view, spontaneous mutations are very beneficial, because they adjust the indicators of a living organism, ensuring its adaptation to changing environmental conditions and eventually the emergence of new species of animals and plants. But another option is also possible, when the mutation turns out to be dangerous for the body, and, being transmitted to descendants, it conceals a disease.
Defective genesGenetic diseases are those diseases whose cause is not in infection and not in accidental malfunctions of the body, but in the "plan" itself, embedded in the DNA molecule.
A person gets the disease from their parents if a mutation has occurred in their genes. Statistics are disappointing: about 70% of the world's population carries a genome with some deviations from the norm. However, the frequency of such violations is not so great. The fact is that for genetic disorders, it is important not only the presence of a modified DNA site, but also its transmission to subsequent generations.
Genetic diseases differ in the mechanism of occurrence and inheritance, among them there are Mendelian, chromosomal, multifactorial and others. Mendelian diseases are inherited in accordance with Mendel's laws (Gregor Johann Mendel, 1822-1884), according to which the dominant characteristics of the parents are manifested in the offspring. Most genetic mutations do not dominate, remain "silent" throughout a person's life. Only if both the mother and the father are carriers of the altered gene, the child will inherit the mutant gene. That is why marriages between members of the same family, as well as within a limited group of people, often lead to the birth of offspring with genetic abnormalities. The Mendelian group also includes diseases associated with sex chromosomes X and Y. For example, fra-X syndrome (fragile X chromosome syndrome), or Martin-Bell syndrome, occurs mainly in boys. The disease is based on changes in the FMR-1 gene associated with an increase in the number of copies of the CGG trinucleotide repeat (cytidine-guanine-guanine). Normally, such a sequence of DNA nucleotides does not exceed 50-54, while in the DNA of a sick person there are up to one and a half thousand repeats.
By the beginning of the third millennium, scientists knew about eleven thousand Mendelian hereditary diseases, and their number is constantly growing. To date, the molecular mechanisms of many defects have also been solved. Thus, when analyzing seven hundred and sixty–seven defective human genes, it was found that six hundred and fifty-eight of them are responsible for the occurrence of only one violation, seventy-one defective gene is responsible for two violations, thirty - for three. There are defective genes that lead to the development of five, six or seven disorders. One insidious mutation in a single gene can lead to a violation of a number of functions! The same fragile X chromosome leads not only to mental retardation, but is also often characterized by myopia, "cleft lip", apnea, scoliosis and cardiovascular disorders.
Violations can be observed not only in the microstructure of genes, as it happens with Mendelian diseases, but also at the macro level. Such deviations are called chromosomal. For example, Down syndrome (John Langdon Down, 1828-1896) – one of the most common disorders of mental development – is associated with the fact that a newborn receives three chromosomes number 21 instead of two. However, in 5-8% of cases, the anomaly is not associated with an extra, third, chromosome, but with its fragment. In the 21st chromosome there is a gene responsible for the production of myoinositol, an excess of which causes mental retardation. Currently, scientists are trying to find a way to normalize the concentration of this substance in the body of patients. But still, the possibility of drug treatment of Down syndrome will not be presented to humanity soon.
Until recently, mainly monogenic diseases, that is, diseases that occur when one gene is disrupted, have been studied. But most hereditary diseases are associated with simultaneous disruption of several genes and certain environmental influences. Such diseases are called multifactorial. For example, several genes have been found whose mutations are associated with the manifestation of Alzheimer's disease. These are the amyloid protein precursor gene (ARP) on chromosome 21, the apolipoprotein E (ApoE) gene on chromosome 19, the presenilin-1 gene on chromosome 14 and the presenilin-2 gene on chromosome 1. Alzheimer's disease (Alois Alzheimer, 1864-1915), diabetes mellitus, epilepsy, heart failure, asthma, schizophrenia are not caused by not only by the "corrupted" genome, but also by unfavorable environmental factors.
The frequency of manifestations of multifactorial diseases among relatives is noticeably higher than among unrelated individuals, but the root cause still remains a mystery.
Many genetic diseases are extremely rare. Today, several hundred disorders are known, which only a few out of millions suffer from, for example, a violation of the thickness of skin or bones, some mental disorders. There are really exotic genetic disorders, such as premature aging syndrome in children, or Hutchinson-Guilford syndrome (Jonathan Hutchinson, 1828-1913; Hastings Gilford, 1861-1941). The reason for it is a genetic mutation, due to which abnormal protein accumulates in cells, which leads to deformation of the cell nucleus. Instability of nuclear membranes causes changes in tissues and accelerates cell death. The symptoms of the disease are dwarfism, baldness, the appearance of wrinkles, hardening of the walls of the arteries and osteoporosis. The life expectancy of children suffering from this rare disease does not exceed 15-17 years.
But Gilles de la Tourette syndrome (Gilles de la Tourette, 1857-1904) is not life-threatening, but it is associated with the discomfort of both the patient and others. With this syndrome, involuntary muscle movements and brain activity occur from time to time, which manifests itself in twitching of the arms, legs and is accompanied by shouting curses.
Perhaps the rarest disease can be called the recently discovered cold sweat syndrome, which affects only a few people in the world. In this disease, sweating occurs at low temperatures, and not in the heat, as in most people. The causes of this syndrome are still unknown, but may be associated with genetic disorders in the development of articular tissue.
It should be noted that rare genetic diseases are very difficult to study. Several dozen people around the world are insufficient statistics for conducting scientific research. In addition, funding organizations are reluctant to allocate funds for the study of rare mutations, since more common diseases cause more harm, and their study is more attractive to the pharmaceutical industry.
Genetic repairTo date, several thousand genes have been identified that cause or condition a predisposition to the development of diseases.
Tests have already been developed all over the world to identify more than five hundred different diseases. So, even in the womb, it is possible to determine the presence or assess the risk of many terrible diseases, including Down syndrome. Couples planning a child can also undergo genetic testing for the storage of "silent" defective genes that can manifest themselves in offspring. However, genetic diagnosis remains an expensive procedure, so screening is usually limited to only a few dozen of the most common diseases. Doctors either detect the disease in the womb, or let you know that the risk of developing the disease after the birth of a child is very high. In such cases, abortion is recommended.
By the way, many doctors agree that miscarriages may be associated with a genetically defective fetus. Thus, the body gets rid of an unviable embryo, or the embryo itself does not develop fully, which leads to abortion. If a woman has already had several miscarriages, then during the next pregnancy, doctors insist on prenatal diagnosis: in such cases, it is likely that the parents transmit a severe genetic disease to the embryos, which leads to frequent miscarriages.
But even for carriers of defective genes, there is hope. Gene therapy is one of the most promising areas of modern medicine. The history of gene therapy began in 1990, when the American geneticist William French Anderson first applied this method to a small patient – a four-year-old girl with immunodeficiency caused by insufficient function of the enzyme adenosine deaminase (ADA). The doctor injected a virus with a gene encoding this enzyme into the girl's body. The patient's cells began to read the viral genome and made up for the lack of HELL. Although the procedure was successful, gene therapy has not yet become widespread. The fact is that the genome of each patient is unique, so a personal approach is required for everyone. In addition, the human genome is constantly mutating. Currently, many clinical trials on gene therapy of various diseases are being conducted in the world, which allows humanity not to lose hope in the fight against thousands of ailments.
Portal "Eternal youth" www.vechnayamolodost.ru08.02.2008