Bad inheritance: Should we be afraid of genetic diseases?
Often we explain certain states with genetics.- sound health "in the father", intolerance of milk "as at grandmother", an excellent voice and hearing "in the great-grandfather". Many diseases are also the easiest to explain with genetics, at the same time, as if discarding responsibility, because we can affect our own way of life, but not genes. Irina Zhegulina, a clinical geneticist at the Atlas Medical Center, told us about what genetics really affects (at least according to proven data) and what mechanisms in DNA distinguish people from each other.
How are chromosomes
Our organism is the most complex construction consisting of bricks-cells. In the nucleus of each cell contains a DNA molecule, a tightly twisted helix - if you unfold it, you get a line two meters long. For the convenience of storing information, DNA molecules are compactly packed as chromosomes - separate blocks - into 23 pairs. Each chromosome in a pair (except for the XY chromosome in males) carries the same genetic information. This ensures data integrity: if something happened in one copy, you can always read the correct information from another.
The DNA molecule itself contains genes that are endless combinations of four nucleotides - A, T, G, and C. They are named after the first letters of the so-called nitrogenous bases that contain - guanine, adenine, thymine, cytosine. Pairs are always formed in a certain way: adenine - with thymine, guanine - with cytosine. It is this pairwise organization of the molecule that allows it to be twisted. A gene is an “instruction” according to which proteins are formed in the body that perform a variety of functions - from building tissues to regulating the fine workings of the brain. Each gene is a sequence of bases, and a gene can consist of several hundred "letters" as well as several millions. For example, a protein that is required for "packing" DNA into chromosomes is encoded by a short gene consisting of 500 base pairs. And one of the longest genes in the body encodes a dystrophin protein (it participates in building muscle tissue) and consists of 2.6 million base pairs.
The entire human genome is 3.2 billion base pairs. However, not all of these are genes. Genes make up only 2%. The remaining 98% is non-coding DNA, about the function of which scientists are still arguing. According to one version, these areas regulate the work of genes, and on the other, they are the so-called genetic load, which increases slightly with each generation.
How mutations arise
Sometimes substitutions occur in the sequence of bases that make up a gene. They can be compared with misspellings in words. Depending on how strongly the "meaning" of a gene word changes, polymorphisms and mutations are distinguished. Mutations are changes that lead to the fact that the body produces a protein with a significantly altered function. For example, with phenylketonuria, a mutation occurs in the gene encoding the enzyme that processes phenylalanine, an amino acid that is found in almost all foods. Due to the "defective" enzyme, the body cannot absorb this amino acid - as a result, it accumulates and has a toxic effect on the nervous system.
If the “meaning” of the gene word changes insignificantly, the protein performs its functions with minor variations. For example, various combinations of such changes - polymorphisms - can determine different colors of the eyes, hair, and even genetic susceptibility to frequent diseases, such as diabetes and heart and vascular diseases.
Mutations can occur not only within the gene, but also in whole chromosomes. Then they are called genomic or chromosomal. These are significant rearrangements (for example, a change in the number of chromosomes), and they lead to serious diseases. For example, in Down syndrome, a person has not two, but three twenty-first chromosomes, and in Shereshevsky-Turner syndrome, the second X chromosome is missing. Mutations can also be in the "castling" of chromosomes - when they change their place or merge. Carriers of such mutations are most often healthy, but the risk of having a child with a severe genetic syndrome is greatly increased.
What are the most frequent hereditary diseases?
Each of us from birth is the carrier of a set of gene mutations. Since each chromosome has a copy, mutations, as a rule, do not make themselves known, and diseases do not develop. However, if two carriers of the genes of the same disease become a pair, then the risk of having a child with the disease is 25%. Actually, for this reason, it is believed that kinship marriages are dangerous - people with similar genetics have a much higher risk of coincidence of mutations.
Every person on average is a healthy carrier for up to ten mutations that are associated with rare genetic diseases - cystic fibrosis, phenylketonuria, Tay-Sachs disease, and many others. The most frequent hereditary diseases are hemochromatosis (mutation in the HFE gene - up to two cases per thousand), cystic fibrosis (mutation in the CFTR gene - up to five cases per thousand), phenylketonuria (mutation in the PAH gene - up to one case per thousand), congenital dysfunction adrenal cortex (mutation in the CYP21 gene - up to one case per thousand), congenital deafness (mutation in the GJB2 gene - up to two cases per thousand), congenital blindness (mutations in different genes - up to one case per thousand), Huntington's chorea (mutation in HTT gene - up to five cases per thousand), neurofibromatosis (mutation I am in the NF1 gene - up to four cases per thousand), polycystic kidney disease (a mutation in the PKD1 gene - up to eight cases per thousand). Such diseases cannot be completely cured, but with the help of therapy, the manifestations of the syndrome can be more or less alleviated, of course, depending on its severity. Since many of these diseases seriously complicate the condition of the child and his entire future life, scientists have developed preventive measures.
Personalized medicine has made available screening genetic tests that allow you to scan the DNA of future parents for mutations associated with genetic diseases. If the mutations identified in the pair are not associated with the same disease, then the risk for the child will be minimal, but if the same mutations are detected, the risk becomes equal to 25% and is regarded as high. The geneticist offers the couple all possible preventive measures so that the child does not inherit these mutations and be born healthy: this could be IVF with a pre-selected healthy embryo for this mutation, prenatal genetic diagnostics, when a sample of embryonic cells is taken from a pregnant woman, or neonatal screening immediately at birth.
Not all mutations are from parents
Mutations can be acquired in the course of life - most often they are studied in oncology. The cells of our body constantly divide, and with each division errors occur, this is a natural process. It is compensated for by special enzymes that restore DNA: they "erase" errors and insert the right elements in their place. Nevertheless, for several reasons, errors can accumulate - and if at least one error persists in the coding part of the genome, this may affect the functioning of proteins, including enzymes. In the case of cancer, such mutations occur in the genes that regulate cell division - as a result, it becomes uncontrolled. The most vulnerable in this regard are tissues where cells divide particularly actively: the intestinal epithelium, lungs, and organs of the reproductive system.
Genomic (chromosomal) mutations can also be acquired. For example, in bone marrow cells, such mutations can lead to the fusion of genes that regulate each other, which disrupts cell division. It is believed that the main factors that can lead to the accumulation of errors is the effect of ionizing radiation (X-rays) in large quantities, the effect of carcinogens when working in hazardous production. Other factors, including ecology, also affect, but to a lesser extent.
What is the role of genetics in frequent diseases?
The most frequent diseases, including atherosclerosis, gout, diabetes, obesity and dental caries, have a certain genetic component. But still they are multifactorial, that is largely due to circumstances, including lifestyle and nutrition. Doctors of any specialty ask whether there have been cases of such diseases in the family in order to find out if there is an increased risk, but you need to understand that the same diabetes mellitus can develop for reasons related to eating habits, even if the relatives did not have it. Conversely, knowledge of their risks helps to take up the lifestyle in time and prevent such diseases.
There is a genetic factor and allergies, but not any - first and foremost is asthma, allergic rhinitis, eczema. Recently, a study has been conducted that linked the genetics and development of the so-called atopic march - a whole group of allergic diseases that usually develop from early childhood, passing one into another or connecting with each other. Today, seven sites in DNA are known that are reliably associated with an increased risk of early eczema in children and asthma associated with bloom allergy. In general, with regard to allergies, serious and lasting changes in health, often progressive, have a genetic basis. If your grandmother occasionally had an allergy to linden blossoms, and your grandfather - to citrus fruits, it is not at all a fact that you will come across this because of heredity. Another allergy is often called intolerance, that is, the inability of the body to properly process various substances. Intolerance (most often lactose, gluten, alcohol, caffeine) is really due to genetics.
People tend to associate with genetics things that are difficult to explain or understand. "You have such a genetics" - this phrase can be heard even from some doctors. According to Irina Zhegulina, many of the conditions really associated with genetics, for example, vulgar ichthyosis, remain without attention and without proper treatment. The states that people formulate by their manifestations, for example, “often a sore throat”, “often a headache - this is a mother” - rather, only common symptoms. First of all, it is necessary to find their reason for prescribing adequate therapy, and not to put up with the imaginary heredity of these frequent conditions.
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