Heredity and predisposition to disease: what you need to know

Chapter 1: Fundamentals of heredity and genetics

1.1. Deoxyribonucleic acid (DNA): the foundation of heredity

DNA, or deoxyribonucleic acid, is a molecule containing genetic instructions for the development, functioning, growth and reproduction of all known living organisms and many viruses. This complex macromolecule is a double spiral consisting of two chains intertwined with each other. Each chain consists of a sequence of nucleotides.

• Nucleotide structure: Each nucleotide consists of three components:

  • Deoxyribose: Five -carbon sugar, forming the basis of nucleotide.
  • Phosphate group: It is attached to 5′-Uglerod deoxyribose and forms a connection with other nucleotide, forming a DNA chain.
  • Nitrogenic base: Anger to 1′-Uglerod deoxyribose. There are four types of nitrogenous bases in DNA:
    • Adenine (a): Purine, always forming a couple with Timine.
    • Guanin (G): Purine, always forming a pair with cytosine.
    • Cytosine (c): Pirimidine, always forming a couple with guanine.
    • Timin (t): Pirimidine, always forming a couple with adenin.

• Principle of complementarity: Two DNA chains are kept together with hydrogen bonds between nitrogenous bases. Adenin (A) always forms a pair with Timin (T) through two hydrogen bonds, and Guanine (G) always forms a couple with cytosin (C) by means of three hydrogen bonds. This is called the principle of complementarity.

• DNA sequence: The sequence of nucleotides in DNA determines genetic information. Various sequences encode different genes, which, in turn, determine the characteristics of the body.

1.2. Genes: units of heredity

The gene is a DNA section containing instructions for the synthesis of a certain protein or RNA molecule. Genes are the main units of heredity and are responsible for the transfer of signs from parents to descendants.

• Gene structure: Genes consist of various elements:

  • Promoter: The DNA area, to which the RNA polymerase is attached to the start of transcription of the gene.
  • Coding area: It contains a sequence of nucleotides, which is transcribed in RNA and then broadcast into protein. This area consists of exons (coding sequences) and intron (non -dodging sequences).
  • Terminator: The DNA area signaling the completion of the transcription of the gene.

• Genes: Genes perform various functions, including:

  • Protein encoding: Most genes encode proteins that perform many functions in a cell, such as enzymes, structural proteins, hormones and antibodies.
  • Regulation of the expression of other genes: Some genes encode RNA molecules that regulate the expression of other genes, controlling their activity.
  • Participation in cell processes: Genes are involved in all cellular processes, such as growth, development, metabolism and reproduction.

1.3. Chromosomes: carriers of genes

Chromosomes are structures consisting of DNA and proteins that carry genes. A person has 46 chromosomes organized in 23 pairs. One chromosome from each pair is inherited from the mother, and the other from the father.

• The structure of the chromosome: Chromosomes consist of DNA, tightly packed around proteins called histones. This packaging allows DNA to fit in the cage core.

  • Center: The area of ​​the chromosome to which the microtubules are attached during the division of the cell.
  • Telomeres: Protective end areas of chromosomes that prevent DNA damage.
  • Shoulders: Two shoulders of chromosomes, one short (p-flecho) and one long (Q-Plecho).

• Types of chromosomes:

  • Autosomes: 22 pairs of chromosomes not related to the definition of gender.
  • Sexual chromosomes: One pair of chromosomes determining the sex of man (XX in women and XY in men).

1.4. Alleles: Genes options

Allele is one of several possible gene options. Each person has two alleles for each gene, one inherited from the mother and one inherited from the father.

• Homozigi and heterozygosity:

  • Homozygotnostx: A condition when a person has two identical alleles for a certain gene.
  • Heterosigo: A condition when a person has two different alleles for a particular gene.

• Dominant and recessive alleles:

  • Dominant allele: The allele, which manifests itself in the phenotype (observed feature) even in a heterozygous state.
  • Recessive allele: Allele, which manifests itself in the phenotype only in a homozygous state.

1.5. Genotype and phenotype

• Genotype: The genetic composition of the body, that is, the totality of all its genes and alleles.
• Phenotype: The observed characteristics of the body, such as growth, eye color, blood type and predisposition to disease. The phenotype is the result of the interaction of the genotype with the environment.

1.6. Mutations: changes in DNA

Mutations are changes in the DNA sequence. They can occur spontaneously or under the influence of external factors, such as radiation or chemicals. Mutations can be harmful, useful or neutral.

• Types of mutations:

  • Particular mutations: Changes in one nucleotide.
    • Replacements: Replacement of a number of nucleotide others.
      • Transitions: Replacing purin with purin (a by g or g on a) or pyrimidine on pyrimidine (C to T or T to C).
      • Transversions: Replacing Purin to Pyrimidine or Pyrimidine on Purin.
    • Inserts: Insert one or more nucleotides.
    • Deletions: Removing one or more nucleotides.
  • Chromosomal mutations: Changes in the structure or number of chromosomes.
    • Deletions: Removing the chromosome site.
    • Duplications: Doubling the site of the chromosome.
    • Inversions: The coup of the chromosome site is 180 degrees.
    • Translocations: Moving the chromosome section to another chromosome.
    • ANEULOIDIDID: Changing the number of chromosomes (for example, trisomy or monosomy).

• Reasons for mutations:

  • Spontaneous mutations: Arise as a result of errors for DNA replication or DNA reparation.
  • Induced mutations: Arise under the influence of mutagenes, such as:
    • Radiation: Ultraviolet radiation, x-ray radiation, gamma radiation.
    • Chemicals: Some chemicals can damage DNA or intervene in the processes of replication or DNA repair.
    • Viruses: Some viruses can be built into the owner’s genome and cause mutations.

Chapter 2: Hereditary diseases

2.1. Classification of hereditary diseases

Hereditary diseases are diseases caused by mutations in genes or chromosomes that are transmitted from parents to descendants. They can be classified according to various criteria:

• By the type of inheritance:

  • Autosomal dominant: The disease manifests itself if a person has at least one mutant allele on an autosome.
  • Autosomal recessive: The disease manifests itself if a person has two mutant alleles on an autosome.
  • X-linked dominant: The disease manifests itself in women if they have at least one mutant allele on the X chromosome, and in men, if they have a mutant allele on the X chromosome.
  • X-linked recessive: The disease manifests itself in men if they have a mutant allele on the X chromosome, and women, if they have two mutant alleles on the X chromosome. Women can be carriers without showing symptoms.
  • Y-linked: The disease is transmitted only from father to son, since the gene is located on the Y chromosome.
  • Mitochondrial: Diseases caused by mutations in mitochondrial DNA are transmitted only from mother to children.

• By type of mutation:

  • Gene mutations: Mutations affecting one gene.
  • Chromosomal mutations: Mutations affecting the structure or number of chromosomes.

• For affected organs and systems:

  • Nervous diseases: Gentington disease, spinal muscle atrophy.
  • Cardiovascular diseases: Family hypercholesterolemia, marfan syndrome.
  • Metabolic diseases: Phenylketonuria, cystic fibrosis.
  • Oncological diseases: Hereditary breast cancer and ovary, hereditary colorectal cancer.

2.2. Autosomal dominant hereditary diseases

With the autosomal-dominant type of inheritance, one mutant allele in the autosoma is enough for the disease to appear. A sick person, as a rule, has one sick parent. The probability of transferring the mutant allele to the descendant is 50%.

• Examples of autosomal dominant diseases:
  • Gentington disease: Neurodegenerative disease, causing a progressive loss of motor, cognitive and psychiatric functions. It usually begins at middle age.
  • Neurofibromatosis of type 1: The disease characterized by the formation of multiple tumors (neurofiber) on the skin, in the nervous system and other organs.
  • Family hypercholesterolemia: The disease characterized by an increased level of cholesterol in the blood, which increases the risk of developing cardiovascular diseases.
  • Marfan syndrome: A disease that affects the connective tissue, which leads to heart problems, blood vessels, eyes and skeleton.
  • Achondroplasia: The form of dwarf, characterized by shortening of the limbs.

2.3. Autosomal recessive hereditary diseases

With an autosomal recessive type of inheritance, the disease is manifested only if a person has two mutant alleles in an autosome. Both parents are carriers of a mutant allele, but they themselves usually do not get sick. The probability of the birth of a sick child in two carrier parents is 25%.

• Examples of autosomal recessive diseases:
  • Cykovyskidosis (cystic fibrosis): The disease that affects the lungs, pancreas and other organs, causing the formation of thick mucus that blocks the respiratory tract and digestive enzymes.
  • Phenylketonuria (FCU): A disease in which the body cannot metabolize phenylalanine, an amino acid contained in food. If you do not treat, FCU can lead to mental retardation.
  • Sickle -cell anemia: Blood disease in which red blood cells have a sickle form, which leads to their destruction and blockage of blood vessels.
  • Talasemia: A group of blood diseases characterized by a decrease in hemoglobin products.
  • Spinal muscle atrophy (SMA): A genetic disease that affects motor neurons, which leads to muscle weakness and atrophy.

2.4. X-linked hereditary diseases

Genes located on the X chromosome are transmitted according to a special mechanism related to the floor. Women have two x chromosomes (XX), and men-one X-chromosome and one Y Cromosome (XY).

• X-linked dominant diseases: The disease manifests itself in women if they have at least one mutant allele on the X chromosome, and in men, if they have a mutant allele on the X chromosome. Women, as a rule, are sick less than men, since they have a second X-chromosome. Examples: Retta syndrome, vitamin-D-resistant rickets.

• X-linked recessive diseases: The disease manifests itself in men if they have a mutant allele on the X chromosome, since they do not have the second X chromosome to compensate for the mutation. Women should have two mutant alleles on the X chromosome to get sick. Women with one mutant allele are carriers and usually do not get sick, but can convey a mutation to their children. Examples: hemophilia, colortonism, muscle dystrophy of Duchenne.

2.5. Y-linked hereditary diseases

Genes located on the Y chromosome are transmitted only from father to son. Y-linked diseases are very rare, since there are relatively few genes on the Y chromosome. An example is male infertility caused by mutations on the Y chromosome.

2.6. Mitochondrial hereditary diseases

Mitochondria is an organella located in cells and are responsible for the production of energy. Mitochondria have their own DNA (MTDNK), which is transmitted only from mother to children. Mitochondrial diseases occur as a result of mutations in MTDNK. All the children of the sick mother will carry a mutation, but the sons do not pass it on to their children. Examples: Leia syndrome, mitochondrial encephalomyopathy with lacticidosis and stroke -like episodes (MELAS).

2.7. Chromosomal diseases

Chromosomal diseases arise as a result of changes in the number or structure of chromosomes. They often lead to serious disorders of development and health.

• Aneuploidii: Changing the number of chromosomes.

  • Trisomy: The presence of three copies of one chromosome instead of two. Examples:
    • Down Syndrome (Trisomy 21): It is characterized by mental retardation, characteristic features of the face and other physical abnormalities.
    • Edwards syndrome (Trisomy 18): A severe disease characterized by numerous congenital defects and a short life expectancy.
    • Patau’s Syndrome (Trisomy 13): A serious disease characterized by multiple congenital defects and a short life expectancy.
  • Monosomy: The absence of one chromosome from the pair. Example:
    • Turner syndrome (monosomy x): It is found only in women and is characterized by low growth, lack of puberty and other health problems.

• Structural chromosomal aberrations: Changes in the structure of chromosomes.

  • Deletions: Removing the chromosome site. Example: cat scream syndrome.
  • Duplications: Doubling the site of the chromosome.
  • Inversions: The coup of the chromosome site is 180 degrees.
  • Translocations: Moving the chromosome section to another chromosome.

Chapter 3: Disease Disease

3.1. Multifactorial diseases

Many common diseases, such as cardiovascular diseases, diabetes, cancer and mental disorders, are multifactorial. This means that they are caused by the interaction of genetic factors and environmental factors.

• Genetic predisposition: The presence of certain genetic options that increase the risk of the development of the disease. These options, as a rule, are common in the population and have a slight influence on the risk of the development of the disease separately. However, in combination with other genetic options and environmental factors, they can significantly increase the risk.
• Environmental factors: They include diet, lifestyle, exposure to toxins and infections. These factors can affect genes and increase or reduce the risk of the development of the disease.

3.2. Our polymorphism is Odnonucleotide (SNP)

Polymorphisms of one -oglotides (SNP) is the most common type of genetic variations in people. SNP are differences in one nucleotide in the DNA sequence. Most SNP have no effect on health, but some SNP can be associated with an increased risk of developing certain diseases.

• SNP effects on the risk of diseases:
  • Influence on the protein function: Some SNP can change the amino acid sequence of protein, which can affect its function.
  • Influence on the expression of the gene: Some SNP can affect the gene expression, increasing or decreasing the amount of protein produced by the genome.
  • Influence on regulatory elements of DNA: Some SNP can affect the regulatory elements of DNA that control the expression of genes.

3.3. Genetic studies of associations (GWAS)

Genetic studies of associations (GWAS) is a method used to identify genetic options (for example, SNP) associated with certain diseases or signs. GWAS analyze the genomes of a large number of people with and without disease in order to identify SNP, which are more common in people with a disease.

• Advantages Gwas:

  • Identification of new genetic risk factors: GWAS allows you to identify new genes and genetic options associated with diseases.
  • Improving the understanding of the biological mechanisms of diseases: The identification of genetic risk factors can help understand the biological mechanisms that underlie diseases.
  • Development of new methods of diagnosis and treatment: The results of GWAS can be used to develop new methods of diagnosis and treatment of diseases.

• Gwas Restrictions:

  • Do not explain most of the heredity of the diseases: Most SNP identified in GWAS have a slight effect on the risk of developing the disease separately.
  • Require large sizes of sample: To identify SNP associated with diseases, large sample sizes are needed.
  • Can identify false positive results: There is a risk of detecting false positive results, especially with small sample sizes.

3.4. Examples of multifactorial diseases with a genetic predisposition

• Cardiovascular diseases: Genetic factors, such as SNP in genes encoding lipoproteins, blood coagulation factors and inflammatory proteins, can increase the risk of cardiovascular diseases. Environmental factors, such as smoking, a high content of saturated fats and lack of physical activity, also play an important role.
• Type 2 diabetes: Genetic factors, such as SNP in the genes involved in the regulation of the level of glucose in the blood and the functions of the beta cells of the pancreas, can increase the risk of type 2 diabetes. Environmental factors, such as obesity, lack of physical activity and a high sugar diet, also play an important role.
• Cancer: Many types of cancer have a genetic predisposition. For example, mutations in the BRCA1 and BRCA2 genes significantly increase the risk of breast cancer and ovaries. Environmental factors, such as smoking, the effect of ultraviolet radiation and diet, also play an important role.
• Mental disorders: Genetic factors, such as SNP in the genes involved in neurotransmission and brain development, can increase the risk of mental disorders, such as schizophrenia, bipolar disorder and depression. Environmental factors, such as stress, injuries and abuse of psychoactive substances, also play an important role.

3.5. Epigenetics: the influence of the environment on the expression of genes

Epigenetics is a study of changes in genes expression that are not associated with changes in the DNA sequence. Epigenetic mechanisms can affect which genes are turned on or off in a cage, and can be changed by environmental factors.

• The main epigenetic mechanisms:

  • DNA methylation: Adding a methyl group to cytosin in DNA. DNA methylation usually leads to shutdown of genes.
  • Modifications of histones: Changes in hystona proteins around which DNA is packed. Histonian modifications can affect the availability of DNA for transcription and, therefore, on the expression of genes.
  • Microrm (Markn): Small RNA molecules that can contact MRNA and block its broadcast into protein.

• The influence of epigenetics on the development of diseases: Epigenetic changes can play an important role in the development of many diseases, including cancer, cardiovascular diseases, diabetes and mental disorders. Environmental factors, such as diet, stress and the effects of toxins, can cause epigenetic changes that increase the risk of developing these diseases.

Chapter 4: Genetic Testing and Consulting

4.1. Types of genetic testing

Genetic testing is an analysis of human DNA to identify genetic options associated with the risk of developing certain diseases or to transmit them to descendants. There are several types of genetic testing, each of which is intended for different purposes.

• Diagnostic testing: It is used to confirm or exclude the diagnosis of a genetic disease in a person with symptoms. This type of testing can help doctors make an accurate diagnosis and develop a treatment plan.
• Predictive testing: It is used to determine the risk of developing a genetic disease in the future in a person without symptoms. This type of testing can help people make informed decisions about their health and lifestyle.
• Prenatal testing: It is used to detect genetic diseases in the fetus during pregnancy. This type of testing can help parents decide on the continuation or termination of pregnancy.
• Newborns screening: It is used to detect genetic diseases in newborns. Early detection and treatment of these diseases can prevent serious complications.
• Testing of carriage: It is used to determine whether a person is a carrier of a mutant gene, which can be transferred to his descendants. This type of testing can be useful for couples planning pregnancy, especially if their family has cases of genetic diseases.
• Pharmacogenetic testing: It is used to determine how a person will respond to certain drugs. This type of testing can help doctors choose the most effective and safe medicine for each patient.
• Testing for the establishment of kinship: Used to determine biological kinship between people.

4.2. Genetic testing methods

For genetic testing, various DNA analysis methods are used. The choice of the method depends on the purpose of testing and the type of genetic options that need to be identified.

• PCR (polymerase chain reaction): A method used for amplification (multiplication) of a certain DNA section. This allows you to get a sufficient amount of DNA for analysis.
• DNA sequencing: The method used to determine the sequence of nucleotides in DNA. DNA sequencing allows you to identify mutations and other genetic options.
• Fish (fluorescent in situ hybridization): The method used to visualize specific DNA sections on chromosomes. Fish can be used to identify chromosomal aberrations, such as deletions, duplication and translocation.
• Microchips (DNA microtics): The method used to simultaneously analyze thousands of genetic options. Microchips can be used to detect SNP, mutations and other genetic changes.
• Eczu sequencing: The method used to sequenize all encoding areas of genes (exom). Eczun sequencing can be used to detect mutations that cause genetic diseases.
• Full -seed sequencing: The method used to sequenize the entire human genome. Full -seed sequencing can provide the most complete information about the genetic variants of a person.

4.3. Genetic counseling

Genetic counseling is a process during which a geneticist or genetic consultant provides information and support to people and families with a risk of a genetic disease or conveying it to descendants.

• Genetic counseling goals:
  • Providing information: An explanation of the nature of a genetic disease, its causes, inheritance and risks for offspring.
  • Risk assessment: Assessment of the risk of developing a genetic disease in a person or his offspring.
  • Discussion of testing options: Discussion of various options for genetic testing, their advantages and restrictions.
  • Decision support: Assistance to people and families to make informed decisions on genetic testing, pregnancy planning and other issues related to genetic disease.
  • Psychological support: Providing psychological support to people and families faced with a genetic disease.

4.4. Ethical and social issues of genetic testing

Genetic testing raises important ethical and social issues.

• Confidentiality: It is necessary to ensure the confidentiality of human genetic information.
• Discrimination: There is a risk of discrimination based on genetic information, for example, in employment or insurance.
• Informed consent: People should be fully informed about the advantages and risks of genetic testing before giving their consent.
• The right not to know: People have the right not to know their genetic information.
• Influence on family relationships: Genetic information can affect family relationships, especially in cases where mutations are detected.
• Availability of testing: It is important to ensure equal access to genetic testing for all, regardless of their socio-economic status.

Chapter 5: Risk Prevention and Management

5.1. Modified risk factors

Although a genetic predisposition plays an important role in the development of many diseases, environmental factors are also of significant importance. Modified risk factors are factors that can be changed or controlled to reduce the risk of the development of the disease.

• Diet: A healthy diet rich in fruits, vegetables and whole grain products can reduce the risk of developing cardiovascular diseases, type 2 diabetes, cancer and other diseases.
• Physical activity: Regular physical activity can improve the health of the heart and blood vessels, reduce blood sugar, strengthen bones and muscles, and improve mood.
• Refusal of smoking: Smoking is the main risk factor for the development of cancer of the lungs, cardiovascular diseases and other diseases. Refusal of smoking significantly reduces the risk of developing these diseases.
• Alcohol use restriction: Excessive alcohol consumption can increase the risk of developing liver diseases, cardiovascular diseases and certain types of cancer.
• Weight control: Obesity and overweight increase the risk of type 2 diabetes, cardiovascular diseases, cancer and other diseases. Maintaining a healthy weight can reduce the risk of developing these diseases.
• Stress management: Chronic stress can increase the risk of developing cardiovascular diseases, depression and other diseases. Stress management using relaxation techniques, meditation or yoga can improve health.
• Regular medical examinations: Regular medical examinations allow you to identify diseases in the early stages, when treatment is most effective.
• Vaccination: Vaccination can protect against many infectious diseases that can lead to serious complications.

5.2. Lifestyle and health

A change in lifestyle can significantly reduce the risk of developing diseases, even in people with a genetic predisposition.

• Balanced nutrition: Eating various foods rich in nutrients can improve health and reduce the risk of diseases. It is important to include fruits, vegetables, whole grain products, low -fat proteins and healthy fats in the diet. The consumption of processed products, sugar and saturated fats should be limited.
• Regular physical exercises: It is recommended to engage in physical exercises of moderate intensity of at least 150 minutes a week or intense exercises of at least 75 minutes a week. Physical activity may include walking, running, swimming, cycling or other sports.
• Refusal of bad habits: Refusal of smoking and excessive alcohol consumption can significantly improve health and reduce the risk of diseases.
• Sufficient sleep: It is recommended to sleep at least 7-8 hours a day. A sufficient dream is important for restoring the body and maintaining health.
• Stress management: It is important to find ways to cope with stress, such as relaxation techniques, meditation, yoga or hobbies.
• Social support: Support from family and friends can help cope with stress and improve health.

5.3. Pharmacological prevention

In some cases, drugs can be used to prevent diseases.

• Statin: Preparations that reduce blood cholesterol can be used to prevent cardiovascular diseases in people with high risk.
• Aspirin: Low doses of aspirin can be used to prevent cardiovascular diseases in people with high risk.
• ACE inhibitors: Preparations that reduce blood pressure can be used to prevent cardiovascular diseases in people with high risk.
• Cancer prevention drugs: Some drugs can be used to prevent cancer in people with high risk, for example, tamoxifen for the prevention of breast cancer.

5.4. Early diagnosis and screening

Early diagnosis and screening allow you to identify diseases in the early stages when treatment is most effective.

• Cancer screening: Regular screening for cancer, such as mammography, colonoscopy and papa test, can detect cancer in the early stages.
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