Heredity and development of diseases: from genes to disease

Heredity and development of diseases: from genes to disease

1. Fundamental principles of heredity

Heredity is the property of organisms to convey their signs and features of development from generation to generation. This process is carried out through genes that are units of hereditary information located on chromosomes. Chromosomes, in turn, consist of DNA (deoxyribonucleic acid), molecules that store the genetic code.

• DNA and genetic code: DNA is a double spiral consisting of nucleotides. Each nucleotide consists of deoxyribose (sugar), phosphate group and nitrogen base. There are four types of nitrogenous bases: adenine (A), Timin (t), guanine (G) and cytosine (C). The sequence of these bases determines the genetic code. Codons – trilles of nucleotides – encode amino acids, which are construction blocks of proteins.

• Genes and alleles: The gene is a DNA section that encodes a certain protein or RNA. Each person inherits two copies of each gene, one from each parent. These copies can be identical (homozygous genotype) or different (heterozygous genotype). Various gene variants are called alleles.

• Chromosomes and their structure: A person has 23 pairs of chromosomes, 22 pairs by autosomes (chromosomes that do not determine the floor) and one pair of sexual chromosomes (XX in women and XY in men). Each chromosome consists of DNA, tightly packed around proteins called histones. The structure of the chromosome provides its compactness and regulates access to genetic information.

• Mitosis and meiosis: Mitosis is a process of dividing somatic (non -head) cells, as a result of which two genetically identical cells are formed. Meiosis is the process of dividing germ cells (gametes), as a result of which four haploid cells are formed (containing one set of chromosomes at one set). Meiosis includes crossingover, the process of exchanging genetic material between homologous chromosomes, which increases genetic diversity.

• Mendelevskoye inheritance: The principles formulated by Gregor Mendel describe the basic patterns of inheritance of signs determined by one genome. These include:

  • The law of the uniformity of the first generation hybrids: When crossing homozygous individuals with alternative signs, all the first generation hybrids are uniform on this basis.
  • The law of splitting signs: When crossing the first generation hybrids in the offspring, there is a splitting of signs in a certain ratio (usually 3: 1 with complete dominance).
  • Independent inheritance law: Genes located on different chromosomes are inherited independently of each other.

2. Types of hereditary diseases

Hereditary diseases are diseases caused by genetic mutations that are transmitted from parents to offspring. There are several types of hereditary diseases, depending on the method of inheritance and the type of mutation.

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

  • Autosomal dominant: One copy of the mutant gene is enough to cause a disease. Each child of the sick parent has 50% risk of inheritance of the disease. Examples: Huntington disease, type 1 neurofibromatosis.
  • Autosomal-recessive: Two copies of the mutant gene are needed to cause a disease. Parents who are carriers of the mutant gene (having one copy) usually do not show symptoms of the disease. Each child of two carrier parents has a 25% risk of getting sick, 50% risk of being a carrier and 25% risk not to inherit a mutant gene. Examples: cystic fibrosis, phenylketonuria.
  • X-linked dominant: The mutant gene is located on the X chromosome. Women with one copy of the mutant gene show symptoms of the disease (albeit less pronounced than that of men). Men with a mutant genome always get sick. All daughters of the sick father inherit the disease. Examples: Vitamin-D-resistant rickets.
  • X-linked recessive: The mutant gene is located on the X chromosome. Men with a mutant genome always get sick. Women with one copy of the mutant gene are usually carriers and do not show the symptoms of the disease (although there may be slight manifestations). A woman gets sick only in the presence of two copies of a mutant gene. Examples: hemophilia, colortonism.
  • Y-linked: The mutant gene is located on the Y chromosome. It is transmitted only from father to son. Examples: some forms of male infertility.

• Mitochondrial diseases: Caused by mutations in mitochondrial DNA (MTDNK). Mitochondria is an organella in cells responsible for the production of energy. MTDNK is transmitted only from mother to children. All children of a sick mother inherit a mutation, but the degree of manifestation of the disease can vary. Examples: Leia syndrome, melas (mitochondrial encephalomyopathy, lactoacidosis and stroke -like episodes).

• Chromosomal diseases: Caused by changes in the amount or structure of chromosomes.

  • ANEULOIDIDID: The presence of an abnormal amount of chromosomes (for example, trisomy – the presence of three copies of the chromosome instead of two). Examples: Down Syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), Patau syndrome (Trisomy 13), Klainfelter syndrome (XXY), Turner syndrome (X0).
  • Structural abnormalities of chromosomes: Changes in the structure of the chromosome, such as deletions (loss of part of the chromosome), duplication (repetition of part of the chromosome), inversion (coup of the chromosome section), translocation (transfer of the chromosome section to another chromosome). Examples: Cat Scream Syndrome (Deletion of a short shoulder of the 5th chromosome), Di Georgie syndrome (Deletion 22q11.2).

• Multifactorial diseases: Caused by the interaction of genetic factors and environmental factors. They are not inherited according to simple Mendelev laws and are often characterized by a family predisposition. Examples: cardiovascular diseases, type 2 diabetes, cancer, asthma, autoimmune diseases.

3. Mutations: Sources of genetic diversity and cause of diseases

Mutations are changes in the DNA sequence. They can occur spontaneously or be caused by the influence of mutagenes (chemicals, radiation, viruses). Mutations are a source of genetic diversity, but can also be the cause of hereditary diseases.

• Types of mutations:

  • Crack mutations: Changes in one nucleotide.
    • Replacements: Replacing one nucleotide to another. Can be:
      • Transitions: Replacing Purin at Purin (a G) or pyrimidine of pyrimidine (c T).
      • Transversions: Replacing purin with pyrimidine or vice versa.
    • Inserts: The insert of one or more nucleotides into the DNA sequence.
    • Deletions: Removal of one or more nucleotides from a DNA sequence.
  • Reading frame shift: The insert or delegation of nucleotide, the number of which is not multiple of three, leads to a shift in the reader and a change in the sequence of amino acids in the protein.
  • Chromosomal mutations: Changes in the structure or quantity of chromosomes (see above).

• The consequences of mutations:

  • Missance Mutation: Replacing nucleotide leads to a replacement of amino acids in a protein. The effect on the protein function can be different – from a slight to complete functional disorder.
  • Nonsense: The replacement of nucleotide leads to the formation of a stop codon, which leads to a premature transaction termination and the formation of a shortened, non-functional protein.
  • Silent-Mutation: Nucleotide replacement does not lead to a change in the amino acid (due to the redundancy of the genetic code) and does not affect the protein function.
  • Mutations in the non -dodging areas of DNA: They can affect the regulation of genes expression, which can also lead to the development of diseases. For example, mutations in the promoter areas of genes can change the level of transcription of the gene.

• Mutagen: Agents that cause mutations.

  • Physical mutagenes: Radiation (ionizing radiation, ultraviolet radiation).
  • Chemical mutagenes: Some chemicals (for example, chainsaw, acridine dyes, nitrosamins).
  • Biological mutagenes: Viruses (for example, hepatitis B virus, human papillomavirus).

4. The role of genes in the development of multifactorial diseases

Multifactorial diseases, such as cardiovascular diseases, type 2 diabetes, cancer and autoimmune diseases, occur as a result of complex interaction of genetic factors and environmental factors. The contribution of each individual gene to the development of these diseases is usually small, but the combined effect of many genes can significantly increase the risk of the development of the disease.

• Distribution genes: Genes that increase the risk of multifactorial diseases. The presence of a predisposition gene does not necessarily lead to the development of the disease, but increases the likelihood of its occurrence when exposed to adverse environmental factors.

• Polymorphisms: Variations in the sequence of DNA, which are found in a population with a frequency of more than 1%. Many polymorphisms do not affect the function of the gene, but some can change the activity of the gene or protein structure, which may affect the risk of the development of the disease. One -okleotide polymorphisms (SNP) are the most common type of polymorphism.

• The study of genes of predisposition:

  • Family research research: An analysis of families in which the disease occurs more often than in a general population allows you to identify genes that are transmitted along with the disease.
  • General association studies (GWAS): Search for associations between DNA polymorphisms and a disease in large groups of people. GWAS allows you to identify new predisposition genes that have not been previously associated with the disease.
  • Meta-analysis: Combining data from several GWAS to increase statistical power and identify weaker genetic effects.

• The interaction of genes and the environment: The effect of genes on the risk of developing the disease may depend on environmental factors. For example, a genetic predisposition to type 2 diabetes can only be manifested in the presence of excess weight and insufficient physical activity.

• Epigenetics: Changes in the expression of genes that are not associated with changes in the DNA sequence. Epigenetic mechanisms, such as DNA methylation and histone modifications, can affect genes and the risk of developing diseases. Environmental factors can affect epigenetic modifications.

5. Genetic testing and counseling

Genetic testing is a DNA analysis for identifying mutations associated with hereditary diseases. Genetic counseling is a process during which a specialist helps patients and their families understand the results of genetic testing, evaluate the risk of developing diseases and make reasonable decisions on treatment and prevention.

• Types of genetic testing:

  • Diagnostic testing: It is carried out to confirm the diagnosis of a hereditary disease in a person who has symptoms of the disease.
  • Presumptomatic testing: It is carried out to identify mutations associated with diseases that develop at a later age (for example, Huntington disease).
  • Predisposition to diseases: Evals the genetic risk of developing multifactorial diseases (for example, breast cancer, Alzheimer disease).
  • Carriage: It determines whether a person is a carrier of a mutant gene associated with a recessive disease.
  • The prenatal diagnostics: It is carried out during pregnancy to detect genetic abnormalities in the fetus. Includes:
    • Amniocentez: Taking a sample of amniotic fluid for the analysis of fetal cells.
    • Chorion Biopsy: Taking a sample of chorion tissue (future placenta) for the analysis of fetal cells.
    • Non -invasive prenatal testing (nipt): Analysis of DNA of the fetus located in the blood of the mother.
  • Newborns screening: It is carried out to identify hereditary diseases that can be treated in the early stages.

• Genetic testing methods:

  • DNA sequencing: Determination of the sequence of nucleotides in DNA. It can be used to identify mutations in specific genes or to analyze the entire genome (full -timing sequencing).
  • PCR (polymerase chain reaction): The amplification method (multiple increase in the quantity) of a specific DNA section.
  • Cariotipirani: Analysis of chromosomes for identifying anneuploidy and structural anomalies of chromosomes.
  • Fish (fluorescent in situ hybridization): The use of fluorescent probes to detect certain DNA sections on chromosomes.
  • DNA microchips: The use of microchips for the analysis of genes expression or to detect DNA polymorphisms.

• Ethical and social issues of genetic testing:

  • Confidentiality: Protecting the genetic information of the patient from unauthorized access.
  • Discrimination: The ban on discrimination based on genetic information (for example, in the field of insurance or employment).
  • Psychological impact: Genetic testing can have a significant psychological effect on the patient and his family.
  • Informed consent: It is necessary to ensure that the patient understands the purpose of genetic testing, his risks and advantages, as well as the consequences of testing results.

6. Gene therapy: Prospects for the treatment of hereditary diseases

Gene therapy is a method of treating hereditary diseases based on the introduction of genetic material to the patient’s cell to correct or compensate for a genetic defect.

• Types of genetic therapy:

  • Introduction of a functional copy of the gene: The introduction of a normal copy of the gene, the function of which is impaired due to mutation.
  • Inactivation of mutant gene: The use of RNA interference technology (RNAI) or CRISPR-CAS9 for the inactivation of the mutant gene.
  • Genoma editing: Using CRISPR-CAS9 technology to correct mutation in cell DNA.

• Generation vectors:

  • Viral vectors: The use of viruses (for example, adenoviruses, lendiviruses, adenoassed viruses) as vectors for the delivery of genes to cells. Viruses are modified so that they cannot multiply in the patients of the patient and do not cause a disease.
  • Nevirus vectors: Use with liposa, nanoparticles or electroporations to deliver genes to cells.

• Methods of introducing genes:

  • In vivo: The introduction of genes directly into the patient’s body.
  • Ex vivo: The capture of cells from the patient, their modification genetically in the laboratory and the return of modified cells to the patient’s body.

• Success of genetic therapy: Gene therapy has shown the effectiveness in the treatment of some hereditary diseases, such as spinal muscle atrophy (SMA), hereditary blindness (Leber Congenital AMAROSISS) and beta-Talassemia.

• Problems of genetic therapy:

  • Immune answer: The introduction of viral vectors can cause an immune response in the patient.
  • Toxicity: Viral vectors can be toxic for patient cells.
  • The risk of integration in the genome: Viral vectors can integrate into the cell of the cell, which can lead to undesirable mutations or activation of oncogenes.
  • Price: Gene therapy is an expensive treatment method.

7. Personalized medicine and genomics

Personalized medicine is an approach to the treatment of diseases that takes into account the individual characteristics of the patient, including his genetic profile, lifestyle and environmental factors. Genomy is a science that studies the structure, function and evolution of genomes. Genomy plays an important role in the development of personalized medicine.

• Pharmacogenomy: The study of the effect of genes on the response of the body to drugs. Pharmacogenomy allows you to select drugs and doses, which will be the most effective and safe for a particular patient.

• Target therapy: Development of drugs that are aimed at specific molecular targets associated with the disease. Genomy helps to identify these molecular targets.

• Diagnostics based on genomic data: The use of genomic data to diagnose diseases in the early stages or to predict the risk of developing diseases.

• Advantages of personalized medicine:

  • More effective treatment: The selection of drugs and doses, taking into account the individual characteristics of the patient.
  • Less side effects: The avoidance of drugs that can cause undesirable side effects in a particular patient.
  • More accurate diagnosis: Diagnosis of diseases in the early stages or predicting the risk of developing diseases.
  • More effective prevention: Development of individual diseases prevention programs, taking into account the genetic predisposition of the patient.

• Problems of personalized medicine:

  • Price: Genomatic testing can be expensive.
  • Data interpretation: The interpretation of genomic data can be a difficult task.
  • Ethical questions: Personalized medicine raises ethical issues related to the confidentiality of genetic information and discrimination based on genetic information.

8. Evolution and hereditary diseases

Evolutionary processes play an important role in the occurrence and maintenance of hereditary diseases. Some mutations that cause diseases can remain in populations if they provide certain advantages in certain environmental conditions.

• Heterozygous advantage: Heterozygous carriers of the mutant gene can have an advantage over homozygous in normal gene. Example: carriers of the Gene of sickle cell anemia are resistant to malaria.

• Genetic drift: Random fluctuations in the frequencies of alleles in the population. Genetic drift can lead to an increase in the frequency of mutant alleles in small populations.

• Founder effect: The emergence of a high frequency of a certain mutant gene in a population that came from a small number of founders.

• The role of the environment: Changing environmental conditions can lead to a change in the frequencies of alleles associated with diseases. For example, the spread of agriculture has led to an increase in the frequency of alleles that ensure the tolerance of lactose in adults.

9. The future of genetics and medicine

Genetics and medicine are on the verge of revolutionary changes. The development of new technologies, such as genomic editing, machine learning and artificial intelligence, opens up new opportunities for the diagnosis, treatment and prevention of diseases.

• Expansion of the use of genomic testing: Genomal testing will become more affordable and common, which will reveal genetic risks of the development of diseases in the early stages.

• Development of new treatment methods: Gene therapy and targeted therapy will become more effective and safe, which will treat many hereditary diseases that were previously considered incurable.

• Preventive genomic: The use of genomic data to develop individual diseases prevention programs.

• Integration of genomics into clinical practice: Genomic data will be integrated into electronic medical cards of patients, which will allow doctors to make more reasonable decisions on the treatment and prevention of diseases.

• Ethical and social issues: It is necessary to solve ethical and social issues related to the use of genetic technologies, such as the confidentiality of genetic information, discrimination based on genetic information and the availability of genetic technologies for all segments of the population.

10. Examples of specific hereditary diseases

• Cymicidosis (Cystic Fibrosis): Autosomal recessive disease caused by mutations in the CFTR gene encoding the chloride canal. Leads to the formation of thick mucus that affects the lungs, pancreas and other organs.

• Sickle Cell Anemia): Autosomal recessive disease caused by a mutation in the beta-globin gene, leading to the formation of abnormal hemoglobin. The red blood cells acquire a sickle form, which leads to chronic anemia, pain and organs.

• Huntington’s Disease. Autosomal-dominant disease caused by the expansion of trinucleotide repetitions of CAG in the HTT gene. Leads to progressive neurodegeneration, causing motor, cognitive and psychiatric disorders.

• Phenylketonuria – PKU): Autosomal recessive disease caused by mutations in the PAH gene, encoding the enzyme phenylalaininghydroxylase. Leads to the accumulation of phenylalanin in the blood, which can cause damage to the brain and mental retardation, if you do not begin treatment (special diet) in early childhood.

• Spinal muscle atrophy. Autosomal recessive disease caused by mutations or deletion of the SMN1 gene, encoding the protein necessary for the survival of motor neurons. Leads to progressive muscle weakness and atrophy.

• Hemophilia (Hemophilia): X-linked recessive disease caused by mutations in genes encoding blood coagulation factors (factor VIII in hemophilia A and factor IX in hemophilia B). Leads to increased bleeding.

• Dauna syndrome (Down Syndrome): Chromosomal disease caused by trisomy according to the 21st chromosome. Leads to mental retardation, characteristic physical characteristics and increased risk of certain diseases.

• Type 1 neurofibromatosis (neurofibromatosis type 1 – nf1): Autosomal dominant disease caused by mutations in the NF1 gene encoding neurofibromin protein. It leads to the formation of tumors (neurofiber) on the nerves, as well as to other problems, such as age spots on the skin (spots of “coffee with milk”) and bone deformations.

These detailed descriptions, while still concise, provide a strong foundation for understanding the complexities of heredity and disease. They also provide keywords for SEO optimization.