Hereditary diseases: how genetics affects health

Hereditary diseases: how genetics affects health

I. Fundamentals of human genetics: the key to understanding hereditary diseases

1. Human genome: drawing of life.

   • DNA: carrier of genetic information. DNA (deoxyribonucleic acid) is a complex molecule containing genetic instructions necessary for the growth, development, functioning and reproduction of living organisms. It is a double spiral consisting of nucleotides, each of which contains a phosphate group, deoxyribosis sugar and nitrogen base (adenine, guanine, cytosine or thyamin). The sequence of these bases determines the genetic code.
   • Chromosomes: Organization of genetic information. DNA is packed in structures called chromosomes. A person in each cell (with the exception of germ cells) contains 23 pairs of chromosomes, only 46. One chromosome from each pair is inherited from the mother, and the other from the father. Chromosomes consist of DNA, tightly packed around proteins called histones.
   • Genes: units of heredity. Genes are DNA segments containing instructions for the production of certain proteins. Proteins perform a wide range of functions in the body, from the construction of tissues and organs to the regulation of chemical reactions. Each gene has a certain location on the chromosome called locus.
   • Genotype and phenotype: the connection between genes and signs. The genotype is a genetic constitution of a person, that is, the totality of all its genes. A phenotype is the observed characteristics of a person, such as growth, eye color and blood group, which are the result of the interaction of the genotype with the environment.

2. Inheritance: transmission of genetic information from parents to descendants.

   • Laws of Mendel: Fundamentals of Genetics. The laws of Mendel, formulated by Gregor Mendel in the 19th century, describe the basic principles of inheritance. These include the law of the uniformity of first -generation hybrids, the law of splitting and the law of independent combination of signs.
   • Autosomal dominant inheritance. With autosomal dominant inheritance, one copy of the mutant gene located on the autosome (non-deciduous chromosome) is enough to make a sign manifest. Each descendant with one parent with a dominant disease has a 50% chance to inherit this disease. An example of such a disease is Huntington’s disease.
   • Autosomalist inheritance. With autosomal recessive inheritance, for the manifestation of a sign, two copies of the mutant gene located on the autosome are necessary. People with only one copy of the mutant gene are carriers and usually do not show signs of the disease. If both parents are carriers, each descendant has a 25% chance to inherit the disease, a 50% chance to become a carrier and a 25% chance not to inherit a mutant gene. An example is cystic fibrosis.
   • X-linked inheritance. X-linked genes are located on the X chromosome. Women have two x chromosomes, and men have one X chromosome and one Y Cromosome. X-linked recessive diseases are more common in men, since they have only one X chromosome. If a man inherits a mutant gene on a X chromosome, he will show a disease. Women can be carriers of x-linked recessive diseases, not showing signs. An example is hemophilia. X-linked dominant diseases manifest both in men and in women, but women can show less severe symptoms due to the presence of two X chromosomes.
   • Mitochondrial inheritance. Mitochondria is organelles inside the cells that produce energy. They have their own DNA, which is inherited only from the mother. Therefore, all the descendants of a woman with mitochondrial disease will inherit this disease.

3. Mutations: a source of genetic variability and diseases.

   • Types of mutations: point, deletions, inherents, duplications, inversions, translocations. Mutations are changes in the DNA sequence. They can occur spontaneously or under the influence of external factors, such as radiation or chemicals. Point mutations are changes in one nucleotide. Deletions are the removal of the DNA segment. Inersion is an insert of DNA segment. Duplication is a repetition of the DNA segment. Inversions are turning the DNA segment. Translocations are the movement of the DNA segment from one chromosome to another.
   • The influence of mutations on the function of genes and proteins. Mutations can affect the function of genes and proteins. Some mutations do not have any influence (neutral mutations). Other mutations can reduce or completely eliminate the function of the gene or protein, which can lead to diseases.
   • Spontaneous mutations and mutations caused by external factors. Spontaneous mutations occur during DNA replication or recombination. Mutations caused by external factors can occur under the influence of radiation, chemicals (mutagen) or viruses.
   • DE NOVO mutations: new mutations that occur for the first time in the family. DE NOVO mutations are new mutations that arise for the first time in the family. They were not inherited from their parents. Such mutations can cause sporadic cases of hereditary diseases.

II. Categories of hereditary diseases: overview of various types of genetic disorders

1. Monogenic diseases: diseases caused by mutation in one gene.

   • Cycle scydosis: violation of the transport of chlorine ions. Cycassocidosis is an autosomal recessive disease caused by mutations in the CFTR gene, which encodes the protein involved in the transport of chlorine ions through cell membranes. This leads to the formation of thick mucus, which affects the lungs, pancreas and other organs. Symptoms include chronic coughing, recurrent lung infections, digestive problems and infertility.
   • Sickle -cell anemia: violation of the structure of hemoglobin. Sickle-cell anemia is an autosomal recessive disease caused by a mutation in the HBB gene, which encodes beta-Globin, a component of hemoglobin. The mutation leads to the formation of abnormal hemoglobin, which deforms red blood cells in a sickle shape. Cherpate cells become brittle and can block blood vessels, causing pain, organs and stroke.
   • Huntington disease: neurodegenerative disease. Huntington disease is an autosomal dominant disease caused by a mutation in the HTT gene, which encodes the Hunting protein. The mutation leads to the formation of an abnormal protein, which accumulates in the brain and causes cell death, especially in basal ganglia. Symptoms include involuntary movements (chorea), cognitive disorders and psychiatric disorders. Symptoms usually begin to appear at the age of 30-50 years.
   • Phenylketonuria (FCU): Violation of metabolism phenylalain. Phenylketonuria is an autosomal recessive disease caused by mutations in the PAH gene, which encodes the enzyme phenylaneineinexylasis. This enzyme is necessary for the transformation of phenylalanine, amino acids coming from food, to Tyrosin. In the absence of a functional enzyme, phenylalanine accumulates in the blood and brain, causing damage to the brain and mental retardation. Early detection and compliance with a strict diet with a low content of phenylalanine can prevent the development of symptoms.

2. Chromosomal diseases: diseases caused by abnormalities in the amount or structure of chromosomes.

   • Down Syndrome (Trisomy 21): the presence of an additional 21st chromosome. Down syndrome is a chromosomal disease caused by the presence of an additional copy of the 21st chromosome (trisomy 21). This leads to characteristic physical features, mental retardation and increased risk of certain medical problems, such as heart defects and Alzheimer’s disease.
   • Turner syndrome (monosomy x): the absence of one X chromosome in women. Turner syndrome is a chromosomal disease that occurs only in women and caused by the absence of one X chromosome (monosomy x) or structural anomalies of one of the X chromosomes. Symptoms include low growth, infertility, heart defects and kidney anomalies.
   • Klainfelter syndrome (XXY): the presence of an additional X-chromosome in men. Klainfelter syndrome is a chromosomal disease that is found only in men and caused by the presence of additional X chromosome (XXY). Symptoms include infertility, high growth, gynecomastia (breast augmentation) and a decrease in testosterone levels.

3. Multifactorial diseases: diseases caused by the interaction of genetic and environmental factors.

   • Type 2 diabetes: Violation of regulation of glucose levels in the blood. Type 2 diabetes mellitus is a multifactorial disease that is characterized by a violation of regulation of blood glucose levels. A genetic predisposition plays a role in the development of this disease, but environmental factors, such as obesity, a sedentary lifestyle and malnutrition, are also important risk factors.
   • Cardiovascular diseases: heart disease and blood vessels. Cardiovascular diseases, such as coronary heart disease and stroke, are multifactorial diseases, the development of which is influenced by genetic and environmental factors. Genetic predisposition, high cholesterol, high blood pressure, smoking and obesity are risk factors.
   • Autoimmune diseases: diseases in which the immune system attacks the body’s own tissues. Autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, are multifactorial diseases, the development of which is affected by genetic and environmental factors. A genetic predisposition to autoimmune diseases can be associated with the genes of the main histocompatibility complex (MHC).
   • Cancer: uncontrolled growth and distribution of abnormal cells. Cancer is a group of multifactorial diseases characterized by uncontrolled growth and the spread of abnormal cells. Genetic mutations can play a role in the development of cancer, but environmental factors, such as smoking, radiation and the effect of chemicals, are also important risk factors. Some types of cancer have a strong hereditary predisposition, for example, breast cancer associated with mutations in BRCA1 and BRCA2 genes.

III. Diagnosis of hereditary diseases: identification of genetic disorders

1. Prenatal diagnosis: detection of genetic diseases in the fetus.

   • Ultrasound examination (ultrasound): fetal visualization. Ultrasound is a non -invasive method that uses sound waves to create an image of the fetus in the womb. Ultrasound can be used to identify certain structural anomalies in the fetus.
   • Amniocentesis: analysis of amniotic fluid. Amniocentesis is an invasive procedure in which a small amount of amniotic fluid is extracted for analysis. Carrostrous waters contain fetal cells, which can be used for genetic analysis, including cariotyping and DNA analysis. Amniocentesis is usually performed between 15 and 20 weeks of pregnancy.
   • Chorion Biopsy (BX): Analysis of the placenta tissue. Chorion’s biopsy is an invasive procedure in which a small sample of the placenta (chorion) fabric is extracted for analysis. The chorion contains fetal cells that can be used for genetic analysis. BX is usually carried out between 10 and 13 weeks of pregnancy.
   • Non -invasive prenatal test (NIPT): analysis of the fetal DNA in the blood of the mother. NIPT is a non -invasive method that analyzes the DNA of the fetus circulating in the blood of the mother. NIPT can be used to identify some chromosomal anomalies, such as Down syndrome, Edwards syndrome and Patau syndrome. NIPT can be carried out already at 10 weeks of pregnancy.

2. Postnatal diagnosis: identification of genetic diseases after birth.

   • Clinical examination and collection of anamnesis: Assessment of symptoms and family history. The clinical examination and collection of an anamnesis are important stages in the diagnosis of hereditary diseases. The doctor will evaluate the symptoms of the patient and collect information about the family history of diseases.
   • Cariotal: analysis of chromosomes. Cariotyping is a method that allows you to visualize and analyze human chromosomes. It is used to identify chromosomal anomalies, such as trisomies, monosomia and translocation.
   • Genetic testing: DNA analysis for identifying mutations. Genetic testing is a DNA analysis that allows you to identify mutations in certain genes. There are various types of genetic tests, including genes sequencing, analysis of microtor and PCR-analysis.
   • Metabolic tests: analysis of the level of certain substances in the blood or urine. Metabolic tests are used to identify metabolism disorders, which can be caused by hereditary diseases such as phenylketonuria.

3. Genetic counseling: providing information and support to families with hereditary diseases.

   • Assessment of the risk of inheritance: determining the probability of transmission of the disease to offspring. The genetic consultant evaluates the risk of inheritance of the disease based on family history, the results of genetic tests and the type of inheritance of the disease.
   • Explanation of the results of genetic testing: providing information about the meaning of the results. The genetic consultant explains the results of genetic testing and their significance for the patient and his family.
   • Discussion of treatment and prevention options: informing about available methods of treatment and prevention. The genetic consultant discusses options for treatment and prevention of the disease, and also provides information about available resources and support.
   • Ethical and social aspects of genetic testing: discussion of confidentiality, discrimination and reproductive decisions. The genetic consultant discusses the ethical and social aspects of genetic testing, such as confidentiality, discrimination and reproductive decisions.

IV. Treatment of hereditary diseases: approaches to the management of genetic disorders

1. Symptomatic treatment: relief of symptoms and improvement of the quality of life.

   • Drug therapy: the use of drugs to control symptoms. Drug therapy is used to control the symptoms of many hereditary diseases. For example, broncholitics and antibiotics are used to treat pulmonary symptoms of cystic fibrosis.
   • Physiotherapy: Improving physical function and mobility. Physiotherapy can be useful for improving physical function and mobility in people with hereditary diseases such as muscle dystrophy.
   • Diet therapy: compliance with a special diet for controlling metabolic disorders. Dietotherapy is an important component of the treatment of many metabolic disorders such as phenylketonuria. Compliance with a strict diet with a low phenylalanine content can prevent the development of FCU symptoms.
   • Rehabilitation: restoration of lost functions. Rehabilitation can help people with hereditary diseases restore lost functions after injury or illness.

2. Gene therapy: the introduction of a normal copy of the gene into the patient’s cells.

   • Types of genetic therapy: vector and non -viral delivery of genes. Gene therapy is an experimental approach to the treatment of hereditary diseases, which includes the introduction of a normal copy of the gene into the patient’s cells. There are various types of genetic therapy, including vector delivery of genes, in which viruses are used as vectors for genu delivery, and non -viral delivery of genes, in which other delivery methods, such as liposomes or electroptions, are used.
   • Clinical trials of genetic therapy: Evaluation of effectiveness and safety. Clinical trials of genetic therapy are carried out to assess the effectiveness and safety of genetic therapy in people with hereditary diseases. Some clinical trials showed promising results, but genetic therapy is still at an early stage of development.
   • Ethical aspects of genetic therapy: discussion of safety issues, accessibility and possible consequences. Gene therapy causes a number of ethical issues, such as safety, accessibility and possible consequences for the future generation.

3. Organ and tissue transplantation: replacement of damaged organs or tissues.

   • Bone marrow transplantation: treatment of blood diseases and immune system. Bone marrow transplantation is used to treat certain diseases of the blood and immune system, such as sickle cell anemia and talassemia.
   • Liver transplantation: treatment of metabolic disorders. Liver transplantation is used to treat some metabolic disorders such as Wilson’s disease.
   • Lung transplantation: treatment of lung diseases, such as cystic fibrosis. Lung transplantation may be a treatment option for people with severe lung diseases, such as cystic fibrosis.

4. Preimplantation genetic diagnostics (PGD): selection of embryos free from genetic diseases.

   • PGD ​​procedure: analysis of embryos before implantation. PGD ​​is a method that is used to analyze embryos for the presence of genetic diseases before implantation in the uterus. During the PGD, the embryo takes one or more cells for genetic analysis.
   • Ethical aspects of the PGD: discussion of the selection of embryos and possible consequences for society. PGD ​​causes a number of ethical issues, such as the selection of embryos and possible consequences for society.

V. Prevention of hereditary diseases: reducing the risk of occurrence and transmission of genetic disorders

1. Genetic counseling: risk assessment and information.

   • Family history: collection of information about diseases in the family. Collection of information about diseases in the family is an important stage in assessing the risk of hereditary diseases.
   • Genetic testing: identification of carriers of mutant genes. Genetic testing can be used to identify carriers of mutant genes that can convey the disease to their children.
   • Reproductive solutions: choosing the most suitable family planning method. Genetic counseling can help families make reasonable reproductive decisions, such as the use of donor sperm or eggs, PGD or rejection of childbearing.

2. Screening of newborns: identification of diseases at an early stage.

   • The purpose of the newborns screening: early detection and treatment of diseases. The goal of screening of newborns is to identify diseases at an early stage, so that you can start treatment before serious symptoms develop.
   • Examples of diseases detected during the screening of newborns: phenylketonuria, congenital hypothyroidism. Examples of diseases detected during newborns screening include phenylketonuria, congenital hypothyroidism and cystic fibrosis.

3. Life and environment: a decrease in the effects of risk factors.

   • Proper nutrition: maintaining healthy weight and consumption of necessary nutrients. Proper nutrition is an important factor in the prevention of many diseases, including some multifactorial hereditary diseases, such as type 2 diabetes and cardiovascular diseases.
   • Physical activity: regular exercises to maintain health. Physical activity is also important for maintaining the health and prevention of many diseases.
   • Avoiding the effects of toxic substances: reducing the risk of mutations. Avoiding the effects of toxic substances, such as smoking and radiation, can reduce the risk of mutations.

VI. The future of genetics and hereditary diseases: new technologies and prospects

1. Genomy: studying the full human genome.

   • Genoma sequencing: Determination of DNA sequence. Genoma sequencing is a process of determining the complete sequence of human DNA. This can be used to identify genetic options that can be associated with the risk of developing diseases.
   • Bioinformatics: analysis and interpretation of genomic data. Bioinformatics is a field of science that is engaged in the analysis and interpretation of genomic data.
   • Personalized medicine: the development of individual approaches to treatment based on the patient’s genetic profile. The genomics opens up new opportunities for personalized medicine, which involves the development of individual approaches to treatment based on the patient’s genetic profile.

2. Genes editing: changes in genes for the treatment of diseases.

   • CRISPR-CAS9: Genes editing technology. CRISPR-CAS9 is a new genes editing technology that allows you to accurately and effectively change the genes in the cells.
   • The use of CRISPR-CAS9 for the treatment of hereditary diseases: potential and risks. CRISPR-CAS9 has a potential for the treatment of many hereditary diseases, but also causes a number of ethical issues related to safety and possible consequences for the future generation.

3. Development of new methods of diagnosis and treatment: Improving the detection and management of hereditary diseases.

   • Development of new genetic tests: more accurate and rapid detection of mutations. New genetic tests are being developed, which are more accurate and quick in the detection of mutations.
   • Development of new drugs: treatment of diseases that were previously incurable. New drugs are being developed that can treat diseases that were previously incurable.

4. Ethical and social issues: discussing complex problems associated with genetic technologies.

   • Confidentiality of genetic information: protection against discrimination. The confidentiality of genetic information is an important problem, since genetic information can be used to discriminate in the field of employment and insurance.
   • Fair access to genetic technologies: providing equal opportunities for everyone. Fair access to genetic technologies is an important issue, since genetic technologies can be expensive and inaccessible to everyone.
   • Regulation of genetic technologies: prevention of abuse. The regulation of genetic technologies is necessary to prevent abuse and ensure their safe and ethical use.