WE ARE FREQUENTLY EXPLAINING THESE OR OTHER STATES BY GENETICS – good health “like a daddy”, milk intolerance “like a grandmother’s”, an excellent voice and hearing “like a great-grandfather.” Many diseases are also the easiest way to explain the genetics, at the same time as it took off from the responsibility – because we can influence their own lifestyle, but not in the genes. About that, on what genetics does influence (at least on the proven data) and what mechanisms DNA distinguish people from one another, we said Irina Zhegulina , MD – Clinical Genetics Medical Center “Atlas”.
How chromosomes work
Our body is a very complex structure, consisting of bricks-cells. The nucleus of each cell contains a DNA molecule, a tightly twisted spiral – if you unfold it, you get a line two meters long. For the convenience of storing information, DNA molecules are compactly packed in the form of chromosomes – separate blocks – in 23 pairs. Each chromosome in a pair (except for the XY chromosome in males) carries the same genetic information. This ensures the safety of the data: if something happened in one copy, you can always read the correct information from the other.
The DNA molecule itself contains genes, which are endless combinations of four nucleotides – A, T, G and C. They are named after the first letters of the so-called nitrogenous bases, which contain – guanine, adenine , thymine , cytosine . Pairs are always formed in a certain way: adenine – with thymine , guanine – with cytosine . It is this paired organization of the molecule that allows it to be twisted. A gene is a “instruction” by which proteins are formed in the body that perform a variety of functions – from building tissues to regulating the fine work of the brain. Each gene is a sequence of bases, and a gene can consist of several hundred “letters” or several million. For example, a protein that is required to “package” DNA into chromosomes is encoded by a short gene of 500 base pairs. And one of the longest genes in the body encodes the protein dystrophin (it is involved in building muscle tissue) and consists of 2.6 million base pairs.
The entire human genome is 3.2 billion base pairs long. However, these are not all genes. Genes are only 2 %. The remaining 98 % is non-coding DNA, the function of which scientists are still debating. According to one version, these areas regulate the work of genes, according to the other , they are the so-called genetic burden, which slightly increases with each generation.
How mutations occur
Sometimes substitutions occur in the sequence of bases that make up a gene. They can be compared to typos in words. In Depending on how much is changing the “meaning” of a gene words, distinguish polymorphisms and mutations. Mutations are changes that lead to the formation of a protein with a significantly altered function in the body. For example, in phenylketonuria , a mutation occurs in a gene that encodes an enzyme that processes phenylalanine , an amino acid 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 insignificant variations. For example, different combinations of such changes – polymorphisms – can determine different color of eyes, hair, and even a genetic predisposition to frequent diseases, such as diabetes mellitus and diseases of the heart and blood vessels.
Mutations can occur not only within a gene, but also in entire 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, with Down syndrome, a person has not two, but three twenty-first chromosomes, and with Shereshevsky – Turner syndrome, the second X chromosome is absent. Mutations can also consist in the “castling” of chromosomes – when they change their place or merge. Carriers of such mutations are most often healthy, but their risk of having a child with a severe genetic syndrome is significantly increased.
What are the most common hereditary diseases
Each of us from birth is a carrier of a set of gene mutations. Since each chromosome has a copy, mutations are usually silent and diseases do not develop. However, if two carriers of 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 family marriages are dangerous – people with similar genetics have a much higher risk of coinciding mutations.
Each person, on average, is a healthy carrier of up to ten mutations that are associated with rare genetic diseases – cystic fibrosis , phenylketonuria , Tay -Sachs disease and many others. The most common 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 in the NF1 gene – up to four cases per thousand), polycystic kidney disease (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 alleviated to a greater or lesser extent – 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 genetic screening tests that scan the DNA of future parents for mutations associated with genetic diseases. If the mutations identified in a couple 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 is born healthy: it can be IVF with a preliminary selection of healthy embryos for a given mutation, prenatal genetic diagnosis, when a sample of cells from a developing embryo is taken from a pregnant woman, or neonatal screening immediately at birth.
Not all mutations are from parents
Mutations can be purchased, and in the course of life – most of them are studying in oncology. The cells of our body are constantly dividing, and with each division errors occur, this is a natural process. It is compensated by special enzymes that restore DNA: they “erase” mistakes and insert the correct elements in their place. Nevertheless, for a number of reasons, errors can accumulate – and if at least one error is preserved in the coding part of the genome, this can 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 especially actively: intestinal epithelium, lungs, 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 are the influence of ionizing radiation (X-rays) in large quantities, exposure to carcinogens when working in hazardous industries. Other factors, including ecology, also affect, but to a lesser extent.
What is the role of genetics in common diseases?
The most common diseases, including atherosclerosis, gout, diabetes, obesity and dental caries, have a genetic component. But they are still multifactorial, that is, they are largely due to circumstances, including lifestyle and nutrition. Doctors of all specialties 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 dietary habits, even if relatives did not have it. And vice versa, knowing your risks helps to take up a lifestyle in time and prevent such diseases.
There is a genetic factor in allergies , but not any – first of all, it is asthma, allergic rhinitis, eczema. Recently, research was conducted that linked genetics and the development of the so-called atopic march – a whole group of allergic diseases that usually develop from early childhood, passing into one another or connecting with each other. Today, there are seven known regions in DNA that are significantly associated with an increased risk of early eczema in children and asthma associated with bloom allergy. In general, when it comes to allergies, serious and persistent health changes, often progressive, have a genetic basis. If your grandmother periodically arose allergy on flowering linden, and from his grandfather – for citrus fruit, not the fact that you will encounter the same by reason of heredity. Allergy is also often called intolerance, that is, the inability of the body to properly process various substances. Intolerance (most often lactose, gluten , alcohol, caffeine) is really caused by genetics.
People tend to associate things with genetics 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 conditions that are really associated with genetics, such as vulgar ichthyosis , are left without attention and without proper treatment. The conditions that people formulate according to their manifestations, for example, “often have a sore throat”, “often have a headache – this is in my mother” – rather, only common symptoms. First of all, it is necessary to find their reason for the appointment of adequate therapy, and not put up with the imaginary heredity of these frequent conditions.