Genetics and human health: inextricable connection

Genetics and human health: inextricable connection

I. Fundamentals of human genetics and its role in health

Genetics is a science that studies the heredity and variability of organisms. In the context of human health, she explores how genetic factors affect the predisposition to diseases, metabolic processes, reaction to drugs and other important aspects of the physiological state. The key concepts underlying this area include:

• DNA (deoxyribonucleic acid): The main carrier of genetic information, which is a double spiral consisting of nucleotides (adenin, thyme, guanine, cytosine). The sequence of these nucleotides determines the genetic code. DNA is compacted in chromosomes.

• Chromosomes: Structures consisting of DNA and proteins located in the core nucleus. In humans, 46 chromosomes organized in 23 pairs (22 pairs with autosomes and one pair of sexual chromosomes – XX in women and XY in men).

• Genes: DNA areas encoding certain proteins or functional RNA. Proteins perform a wide range of functions in the body, from structural components to enzymes that catalyze biochemical reactions. Not all DNA encodes proteins; A significant part of the genome performs regulatory functions.

• Genome: A complete set of organism genetic information, including all genes and non -dodging areas of DNA. The decoding of the human genome within the framework of the “human genome” project has become a turning point in the development of genetics and medicine.

• Allleli: Various gene variants located in the same locus (place) on the chromosome. A person inherits one allele from each parent for each gene.

• Genotype: The genetic composition of the body, determined by a set of alleles for a particular gene or set of genes.

• Phenotype: The observed characteristics of the body, such as eye color, growth, predisposition to certain diseases. The phenotype is the result of the interaction of the genotype and environmental factors.

• Heredity: Transfer of genetic information from parents to offspring. The laws of heredity formulated by Gregor Mendel are the basis of an understanding of how different signs are inherited.

• Variability: Differences in genetic information between individuals. Variability can occur as a result of mutations, recombination and other processes.

• Mutations: Changes in the sequence of DNA. Mutations can be spontaneous or induced environmental factors (for example, radiation, chemicals). Some mutations do not have any effect on the body, others can be harmful, and in rare cases – useful.

• Polymorphism: The presence of several gene alleles in the population with a frequency exceeding a certain threshold (usually 1%). Polymorphisms can be associated with a predisposition to diseases or differences in the reaction to the drugs. Especially important are one -okleotide polymorphisms (SNP).

II. Types of genetic diseases and mechanisms of their inheritance

Genetic diseases occur as a result of mutations or abnormalities in genes or chromosomes. They can be inherited from parents or arise spontaneously. There are several basic types of genetic diseases:

• Monogenic diseases: Called by a mutation in one gene. Types of inheritance of monogenic diseases:

  • Autosomal dominant: The disease manifests itself if a person has at least one copy of the mutant gene on an autosome (not a sexual chromosome). Examples: Huntington disease, neurofibromatosis.

  • Autosoma-RESPECTIVE: The disease is manifested only if a person has two copies of a mutant gene on an autosome. Parents are carriers of a mutant gene, but they themselves do not get sick. Examples: cystic fibrosis, phenylketonuria, sickle cell anemia.

  • X-linked dominant: The disease is manifested in women with at least one copy of the mutant gene on the X chromosome, and in men who have one copy of the mutant gene on the X chromosome. Examples: Vitamin-D-resistant rickets.

  • X-linked recessive: The disease is manifested in men who have one copy of the mutant gene on the X chromosome. In women, the disease manifests itself only if they have two copies of the mutant gene on the X chromosome. Women with one copy of the mutant gene are carriers. Examples: hemophilia, colortonism, muscle dystrophy of Duchenne.

  • Y-set: The disease is transmitted only from father to son, since only men have a Y chromosome. Examples: some forms of male infertility.

  • Mitochondrial inheritance: Mitochondria, organelles in cells with their own DNA. Mitochondrial diseases are transmitted only from mother to offspring, since sperm does not bring mitochondria into the zygote. Examples: mitochondrial myopathy.

• Chromosomal diseases: They are caused by anomalies in the amount or structure of chromosomes. Types of chromosomal anomalies:

  • ANEULOIDIDID: The presence of a wrong number of chromosomes. The most common examples: trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau syndrome), monosomy x (Turner syndrome).

  • Deletions: Loss of part of the chromosome. Examples: Cat Scream Syndrome (deletion of part of the short shoulder of the 5th chromosome).

  • Duplications: Doubling part of the chromosome.

  • Inversions: The coup of the chromosome site is 180 degrees.

  • Translocations: Moving the chromosome section to another chromosome.

• Multifactorial diseases: They are caused by the interaction of genetic factors and environmental factors. These diseases do not obey the simple laws of inheritance, as monogenic diseases. Examples: cardiovascular diseases, type 2 diabetes, cancer, asthma, schizophrenia. The risk of developing a multifactorial disease depends on the genetic predisposition (polygenic risk) and the effects of environmental factors (diet, lifestyle, toxins). Studies of the genome-cheese associations (GWAS) help to identify genetic options associated with multifactorial diseases.

• Epigenetic diseases: They are caused by changes in genes expression not associated with changes in the DNA sequence. Epigenetic changes can be caused by environmental factors and can be inherited. Examples: some types of cancer. The mechanisms of epigenetic regulation include DNA methylation, histone modifications and micrord regulation.

III. Genetic testing and counseling

Genetic testing is an analysis of DNA, RNA or chromosomes to identify genetic changes associated with the disease or predisposition to the disease. Genetic counseling is a process during which patients and their families receive information about genetic diseases, risks of their inheritance, genetic testing and risk management methods.

• Types of genetic testing:

  • Prenatal testing: It is carried out during pregnancy to detect genetic abnormalities in the fetus. Prenatal testing methods:

    • Screening of the first trimester: A combined test, including an ultrasound examination (measurement of the thickness of the collar zone) and a blood test (determining the levels of PAPP-A and free beta-HCH). Allows you to evaluate the risk of Down syndrome, Edwards and Patau.

    • Non -invasive prenatal test (NIPT): Analysis of DNA of the fetus circulating in the blood of the mother. Allows you to identify trisomies according to chromosomes 21, 18 and 13, as well as determine the gender of the fetus. NIPT is a high -precision screening method.

    • Amniocentez: The fence of an amniotic fluid surrounding the fetus is for the analysis of fetal cells. It is usually carried out at 15-20 weeks of pregnancy. Allows you to identify chromosomal abnormalities, monogenic diseases and defects of the nervous tube. Amniocentesis is an invasive method and is associated with a small risk of miscarriage.

    • Chorion Biopsy: The fabric of the chorion tissue (future placenta) for the analysis of fetal cells. It is usually carried out at 10-12 weeks of pregnancy. Allows you to identify chromosomal abnormalities and monogenic diseases. Chorion’s biopsy is an invasive method and is associated with a small risk of miscarriage.

  • Testing of newborns (neonatal screening): It is carried out shortly after birth to detect diseases that can be treated at an early stage. Examples of diseases detected with neonatal screening: phenylketonuria, congenital hypothyroidism, cystic fibrosis.

  • Diagnostic testing: It is carried out to confirm or exclude the diagnosis of a genetic disease in a person with symptoms.

  • Testing of carriage: It is carried out to identify people who are carriers of a mutant gene associated with a recessive disease. Especially useful for couples planning pregnancy for assessing the risk of a child with a disease.

  • Predictive testing: It is carried out to identify a genetic predisposition to diseases that can develop in the future. Examples: Testing on mutations of BRCA1 and BRCA2 genes associated with an increased risk of breast and ovary cancer, testing for the HD gene, associated with Huntington’s disease.

  • Pharmacogenetic testing: It is carried out to determine the genetic options that affect the reaction of a person to medicines. Allows you to choose the most effective and safe dose of drugs, as well as avoid side effects.

  • Genomatic testing: Analysis of the entire human genome to identify genetic options associated with various diseases and signs. Genomal testing can be useful for the diagnosis of complex diseases, determine the predisposition to diseases and the selection of individual treatment.

• Genetic testing methods:

  • Cytogenetic analysis (karyotyping): Visualization of chromosomes under a microscope to detect chromosomal abnormalities (aneuploidia, delections, duplications, inversions, translocations).

  • Fluorescence hybridization in situ (fish): The use of fluorescent DNA zones to identify specific DNA sequences on chromosomes. Allows you to identify microelements and microduplikes.

  • Polymerase chain reaction (PCR): An increase in the number of a specific DNA section for further analysis. Used to identify mutations in genes.

  • DNA sequencing (new generation sequencing, NGS): Determination of the sequence of nucleotides DNA. Allows you to identify mutations in genes, polymorphisms and other genetic options. NGS is used for genomic testing, eccentric sequencing (analysis of the encoding part of the genome) and targeted sequencing (analysis of certain genes).

  • Microting analysis (DNA micro): Determination of the relative number of certain DNA sequences. It is used to identify changes in the expression of genes and to detect microelements and microduplucks.

• Ethical aspects of genetic testing:

  • Confidentiality: Protecting the genetic information of the patient from unauthorized access.

  • Informed consent: Obtaining the patient’s consent to conduct genetic testing after providing complete information about testing goals, possible results and risks.

  • Discrimination: The ban on discrimination based on genetic information in the field of employment, insurance and other areas.

  • Psychological consequences: The provision of psychological support to patients who have received the results of genetic testing, especially if the results are unfavorable.

IV. Genetics and prevention of diseases

Genetic knowledge can be used to develop diseases prevention strategies. The main directions:

• Genetic counseling and family planning: The provision of information on the risks of inheritance of genetic diseases and the possibilities of prenatal diagnostics allows pairs to make conscious decisions on family planning.

• Personalized medicine: The use of genetic information to select individual treatment and prevention of diseases. Pharmacogenetic testing allows optimizing drug therapy. Genetic testing for a predisposition to diseases allows you to develop individual preventive programs.

• Life change change: For people with a genetic predisposition to certain diseases, a change in lifestyle (diet, physical activity, refusal of smoking) can reduce the risk of the development of the disease. For example, people with a genetic predisposition to cardiovascular diseases are recommended to observe a healthy diet and regularly engage in physical exercises.

• Gene therapy: The introduction of genes into human cells that compensate for defective genes or modulate the expression of genes. Gene therapy is under development and can become an effective method of treating genetic diseases.

• Genoma editing (CRISPR-CAS9): Technology that allows you to accurately edit the DNA sequence. The genome can be used to correct mutations that cause genetic diseases. However, the use of genome editing is fraught with ethical problems.

V. Genetics and treatment of diseases

Genetics plays an important role in the development of new methods of treating diseases.

• Target Cancer Therapy: The use of drugs that are aimed at specific genetic changes in cancer cells. For example, drugs that block EGFR (an epidermal growth factor receptor) are used to treat lung cancer with mutations in the EGFR gene.

• Cancer immunotherapy: The use of the body’s immune system to combat cancer. Some types of immunotherapy are aimed at genetic changes in cancer cells that allow them to avoid an immune response.

• Feet -replacement therapy: The introduction of enzymes that they do not have due to a genetic defect. Used to treat some lysosomal accumulation diseases.

• Bone marrow transplantation: Replacing defective hematopoietic cells with healthy ones. It is used to treat some genetic diseases of the blood, such as sickle cell anemia and talassemia.

• Personalized medicine based on genomic data: The use of genomic information to select the most effective treatment for each patient. For example, genomic testing of cancer cells allows you to choose drugs that will most likely be effective in a particular case.

VI. Examples of specific diseases and their genetic basis

• MukoviScidoz: Autosomal recessive disease caused by mutations in the CFTR gene (transmembrane conduction regulator of cystic fibrosis). The CFTR gene encodes a protein that regulates the transport of chlorides through cell membranes. Mutations in the CFTR gene lead to a violation of the transport of chlorides, which leads to the formation of thick mucus in the lungs, pancreas and other organs. Treatment of cystic fibrosis includes physiotherapy, antibiotics, mucolytics and drugs that improve CFTR.

• Phenylketonuria: Autosomal recessive disease caused by mutations in the PAH gene (phenylaneinerydroxylase). The PAH gene encodes an enzyme that turns phenylalanine into tyrosine. Mutations in the PAH gene lead to the accumulation of phenylalanine in the blood, which can lead to damage to the brain. Treatment of phenylketonuria includes compliance with a low phenylalanine diet.

• Huntington disease: Autosomalum-dominant disease caused by the expansion of trinucleotide repetitions (CAG) in the HTT gene (Hunting). An increase in the number of CAG repetitions leads to the formation of an abnormal HuntingTin protein that damages nerve cells in the brain. Huntington’s disease is characterized by progressive motor disorders, cognitive disorders and psychiatric symptoms. There is no treatment that can stop or slow down the progression of Huntington’s disease.

• Sickle -cell anemia: Autosomal recessive disease caused by a mutation in the HBB gene (beta-globin). A mutation in the HBB gene leads to the formation of abnormal hemoglobin, which deforms red blood cells, giving them a sickle form. Cherpate red blood cells can get stuck in small blood vessels, which leads to pain, organs damage and other complications. Treatment of sickle cell anemia includes blood transfusion, painkillers and hydroxymochevin.

• Down syndrome: Chromosomal disease caused by trisomy according to chromosome 21. People with Down syndrome have characteristic physical characteristics, mental retardation and increased risk of developing certain diseases, such as heart defects and Alzheimer’s disease. Treatment of Down syndrome is aimed at improving the quality of life and includes educational programs, physiotherapy and treatment of related diseases.

• Breast cancer (BRCA1/BRCA2): Mutations in the BRCA1 and BRCA2 genes significantly increase the risk of developing breast cancer and ovaries. Women with mutations in these genes are recommended to conduct preventive examinations and consider the possibility of preventive mastctomy and ovarioctomy.

VII. The future of genetics and its effect on human health

Genetics continues to develop rapidly, and its influence on human health will only increase. Expected directions of development:

• More accurate diagnosis of genetic diseases: The development of genomic technologies will more accurately and quickly diagnose genetic diseases, which will allow treatment at an early stage.

• Development of new methods of treating genetic diseases: Gene therapy and editing of the genome promise a revolution in the treatment of genetic diseases.

• Personalized medicine based on genomic data: Genomic information will become the basis for the selection of individual treatment and the prevention of diseases, which will increase the effectiveness of treatment and reduce the risk of side effects.

• Prediction of the risk of developing diseases: Genetic testing will predict the risk of various diseases, which will allow you to take preventive measures and reduce the risk of the disease.

• Improving public health: Genetic knowledge will be used to develop public health programs aimed at preventing diseases and improving the health of the population.

VIII. Restrictions and challenges in the use of genetics

Despite the huge potential, the use of genetics in healthcare is associated with some restrictions and challenges:

• High cost of genetic testing and treatment: Genetic testing and treatment can be very expensive, which makes them inaccessible to many people.

• The uncertainty of genetic testing results: Some genetic tests give vague results, which may make it difficult to make decisions on treatment and prevention.

• Ethical problems: The use of genetics raises ethical issues related to confidentiality, discrimination and Eugenica.

• Lack of qualified specialists: There are not enough qualified geneticists and genetic consultants to conduct genetic testing and interpretation of results.

• The difficulty of interpretation of genomic data: The interpretation of genomic data is a complex task that requires special knowledge and experience.

Overcoming these restrictions and challenges will fully realize the potential of genetics to improve human health.