The effect of genes on a predisposition to diseases

Posted on by

The influence of genes on a predisposition to diseases: extensive review

I. Fundamentals of genetic predisposition:

  1. Human genome: drawing of health and illness.

    • Structure and functions: Description of DNA, chromosomes, genes and their role in encoding proteins, regulating processes in the cell and forming the body. Explanation of transcription and broadcasting principles.
    • Genetic variability: Polymorphisms (SNPS, Indels, CNVS) as the basis of individual differences. The frequency of alleles in populations. The role of mutations in the emergence of new options.
    • Epigenetics: Modifications of DNA and histones that do not change the sequence of nucleotides, but affect the expression of genes. DNA methylation, acetylation of histones and their role in the development of diseases.

  2. Heredity and diseases: the connection of generations.

    • Types of inheritance: Autosomal-dominant, autosomal-recessive, X-setting dominant, X-set recessive, mitochondrial. Examples of diseases transmitted by each of these methods.
    • Genetic consultation: Assessment of the risk of inheritance of diseases based on family history. Genetic testing methods to identify carriage or the presence of mutations.
    • Penetrance and expressiveness: Explanation of the variability of the manifestation of genetic diseases. Penetransiness as a probability of the manifestation of the disease in the presence of a mutation. Expressiveness as the severity of the disease.

  3. Multifactorial diseases: complex interaction.

    • The role of genes and the environment: A combination of genetic predisposition and environmental factors (diet, lifestyle, exposure to toxins, infections) in the development of most common diseases.
    • Polygenic inheritance: The influence of many genes, each of which makes a small contribution to the risk of developing the disease. Examples of polygenic diseases: type 2 diabetes, cardiovascular diseases, cancer, autoimmune diseases.
    • The interaction of the gene-converting environment: Different genotypes can react differently to the same environmental factors. Examples: the effect of smoking on the risk of lung cancer in people with certain genetic options.

II. Genetic predisposition to specific diseases:

  1. Cardiovascular diseases (SVP): Genes and heart health.

    • Atherosclerosis: Genes affecting lipid metabolism (APOE, LDLR), inflammation (IL-6), blood coagulation (F5, F2) and blood pressure (ACE).
    • Corny heart (coronary heart disease): Genetic options associated with the risk of IBS development, such as 9P21.3, LPA, PCSK9.
    • Cardiomyopathy: Genes encoding sarcomer proteins (Myh7, Mybpc3, TPM1), Desmos (Des, PKP2) and ion channels (SCN5A, KCNQ1).
    • Congenital heart defects: Genes participating in the development of the heart (TBX5, NKX2-5, GATA4).
    • Hereditary arrhythmias: Genes encoding ion channels (KCNH2, Scn5A, KCNE1).
    • Genetic testing at the CVD: Identification of patients with high genetic risk for preventive measures.
    • Pharmacogenetics in cardiology: The influence of genetic options on the effectiveness and safety of drugs used for the treatment of CVD (clopidogrel, warfarin).

  2. Oncological diseases: cancer genetics.

    • Tumor Suppressors genes: TP53, BRCA1, BRCA2, PTEN, RB1. Mutations in these genes lead to the loss of their functions and an increase in the risk of cancer.
    • Oncogenes: Ras, Myc, Egfr, Her2. Activation of these genes contributes to uncontrolled cell growth.
    • DNA reparation genes: Mlh1, MSH2, MSH6, PMS2. Mutations in these genes lead to a violation of DNA reparation and an increase in the risk of cancer.
    • Hereditary cancerous syndromes: Lee-frane syndrome (TP53), hereditary breast cancer and ovary (BRCA1/2), linch syndrome (MLH1, MSH2, MSH6, PMS2), family adenomatous polyposis (APC).
    • Genetic testing for oncological diseases: Identification of patients with high genetic risk for preventive measures, early diagnosis and development of individual treatment tactics.
    • Target therapy: The use of drugs aimed at specific genetic mutations in tumor cells (for example, EGFR inhibitors for lung cancer, HER2 inhibitors for breast cancer).
    • Immunotherapy: Activation of the immune system to combat cancer cells. Genetic factors can affect the response to immunotherapy.

  3. Diabetes: Genes and glucose metabolism.

    • Type 1 diabetes (T1D): The genes associated with the immune system (HLA) play a key role in the development of T1D. Insulite, autoimmune destruction of the pancreatic beta-cells.
    • Type 2 diabetes (T2D): Polygenic disease associated with many genes affecting the secretion of insulin (TCF7L2, KCNJ11), insulin sensitivity (PPARG, IRS1) and glucose metabolism (GCK).
    • Monogenic forms of diabetes: MODY (MATURITY -ONSET Diabetes of the Young)-rare forms of diabetes caused by mutations in separate genes (GCK, HNF1A, HNF4A). Neonatal diabetes (KCNJ11, ABCC8).
    • Genetic testing in diabetes: Diagnosis of monogenic forms of diabetes, risk assessment of T2D development.
    • Pharmacogenetics in diabetology: The influence of genetic options on the effectiveness and safety of drugs used to treat diabetes (metformin, sulfonylmochevin).

  4. Neurodegenerative diseases: genes and brain.

    • Alzheimer’s disease: APOE (especially the ε4 allele) is the most powerful genetic factor in the risk of developing Alzheimer’s disease. App, psen1, psen2 – genes associated with the early onset of Alzheimer’s disease.
    • Parkinson’s disease: SNCA, LRRK2, PARK2, PINK1, DJ-1 are genes in which are associated with the development of Parkinson’s disease.
    • Huntington disease: HTT-a mutation in the HTT gene (an increase in the number of CAG-re-transplants) leads to the development of Huntington’s disease.
    • Lateral amyotrophic sclerosis (bass): SOD1, C9orF72, Tardbp, FUS – genes in which are associated with the development of bass.
    • Genetic testing with neurodegenerative diseases: Diagnosis of hereditary forms of diseases, risk assessment of diseases.
    • Development of drugs: Targeted therapy aimed at specific genetic mutations (for example, drugs that reduce the level of mutant protein of HuntingTin).

  5. Autoimmune diseases: genes and immune system.

    • Rheumatoid arthritis (RA): HLA-DRB1 is the main genetic risk factor for the development of RA. PTPN22, CTLA4, StAT4 – other genes associated with RA.
    • System red lupus (SLE): HLA, IRF5, StAT4, BLK – genes associated with SLE.
    • Scattered sclerosis (RS): HLA-DRB1*1501-the main genetic risk factor for the development of RS. IL2RA, IL7R – other genes associated with RS.
    • Inflammatory diseases of the intestine (BCC): NOD2, IL23R, ATG16L1 – genes associated with Crohn’s disease and ulcerative colitis.
    • Genetic testing in autoimmune diseases: Risk of the development of diseases, differential diagnosis.
    • Target therapy: The use of drugs aimed at specific molecules involved in the immune response (for example, TNF-α inhibitors for RA and BAC).

  6. Mental illness: genes and brain.

    • Schizophrenia: A polygenic disease associated with many genes, each of which makes a small contribution to the risk of developing the disease. DRD2, GRM3, DISC1 – examples of genes associated with schizophrenia.
    • Bipolar disorder: Polygenic disease associated with many genes. Ank3, Cacna1c – examples of genes associated with bipolar disorder.
    • Depression: Polygenic disease associated with many genes. SLC6A4 (conveyor gene of serotonin) is an example of a gene related to depression.
    • Autism: Polygenic disease associated with many genes. Some genes, such as Shank3, CHD8 and MECP2, have a stronger connection with autism.
    • Genetic testing in mental illness: Risk of the development of diseases, differential diagnosis. Currently, genetic testing in mental illness is at the stage of research and is not widely used in clinical practice.
    • Pharmacogenetics in psychiatry: The influence of genetic options on the effectiveness and safety of drugs used to treat mental illness (antidepressants, antipsychotic).

  7. Infectious diseases: genes and an immune response.

    • HIV infection: CCR5 – Deletion in the CCR5 gene (CCR5δ32) provides protection against HIV infection. HLA-certain HLA alleles are associated with slower progression of HIV infection.
    • Hepatitis B and C: IL28B – Genetic options in the IL28B gene affect the response to hepatitis C treatment with interferon.
    • Tuberculosis: SLC11A1, VDR – genes that affect the susceptibility to tuberculosis.
    • Malaria: Genes encoding hemoglobin (HBS – sickle cell anemia) provide protection against severe malaria.
    • Genetic testing for infectious diseases: Assessment of the risk of infection, forecasting the course of the disease, determining the optimal tactics of treatment.
    • Vaccines development: The use of genetic information to develop more effective vaccines.

  8. Rare genetic diseases: unique mutations.

    • Cykovyskidosis (cystic fibrosis): CFTR – mutations in the CFTR gene lead to a violation of transport of chlorine ions and the development of cystic fibrosis.
    • Phenylketonuria (FCU): PAH – mutations in the PAH gene lead to a violation of phenylalanine metabolism and the development of FCU.
    • Spinal muscle atrophy (SMA): SMN1 – deletions or mutations in the SMN1 gene lead to a SMN protein deficiency and the development of SMN.
    • Down Syndrome (Trisomy 21): The presence of an additional copy of the 21st chromosome.
    • Turner syndrome (monosomy x): The absence of one X-chromosome in women.
    • Genetic testing for rare diseases: Diagnosis of diseases, determining the carriage of mutations, genetic consultation.
    • Development of drugs: Gene therapy, enzyme-off-off therapy-new approaches to the treatment of rare genetic diseases.

III. Methods of studying genetic predisposition:

  1. Family research:

    • Analysis of the pedigree: The construction of pedigree to identify the laws of inheritance of diseases. Determination of the type of inheritance (autosomal dominant, autosomal recessive, X-settled).
    • Gemini research: Comparison of concordantity (similarities) in diseases in monozygous (single -eating) and dizigative (bilingual) twins to assess the role of genetic and environmental factors.

  2. Association research:

    • GWAS (Genome-Wide Association Studies): The full -genomic search for associations is to scan the entire genome to detect genetic options (SNP), statistically related to the disease.
    • Candidate Genes: The study of associations between specific genes, the function of which is allegedly related to the disease, and the risk of developing this disease.

  3. Full -beam sequencing (WGS) and full -explosive sequencing (WES):

    • WGS: Determination of the complete sequence of the genome.
    • WES: Determination of the sequence of all exons (coding areas) of the genome.
    • Application in research: Identification of new genes and mutations associated with diseases. Personalized medicine.

  4. Bioinformatics and data analysis:

    • Working with big data: Analysis of huge volumes of genetic data.
    • Algorithm development: Creating algorithms to identify genetic options associated with diseases.
    • Data integration: The combination of genetic data with data on environmental factors and lifestyle for a more accurate assessment of the risk of the development of diseases.

  5. Animal modeling:

    • Genetically modified animals: Creation of animals with certain genetic mutations to study the mechanisms of the development of diseases.
    • Transgene models: The introduction of human genes associated with diseases in the genome.

IV. Genetic testing: tool for assessing risks and prevention.

  1. Types of genetic testing:

    • Diagnostic testing: Confirmation of the diagnosis of the disease.
    • Predictive testing: Assessment of the risk of the development of the disease in the future.
    • Presumptomatic testing: Identification of mutations in people who do not have symptoms of the disease, but have a risk of its development (for example, Huntington’s disease).
    • Testing of carriage: The definition is whether a person is a carrier of a mutation that can be conveyed to his offspring.
    • Pharmacogenetic testing: Determination of how genetic versions of a person affect his response to drugs.
    • Prenatal testing: Identification of genetic diseases in the fetus during pregnancy.
    • Preimplantation genetic diagnostics (PGD): Identification of genetic diseases in embryos created as a result of IVF before implantation into the uterus.

  2. Application of genetic testing:

    • Assessment of the risk of developing diseases: Identification of people with a high genetic risk of developing diseases for preventive measures.
    • Differential diagnosis: Clarification of the diagnosis in case of suspicion of a genetic disease.
    • Family planning: Assessment of the risk of the birth of a child with a genetic disease.
    • Personalized medicine: The choice of the most effective and safe treatment based on the genetic data of the patient.

  3. Ethical and social aspects of genetic testing:

    • Confidentiality: Protection of genetic information.
    • Discrimination: Prevention of discrimination based on genetic information (for example, in the field of insurance and employment).
    • Psychological consequences: Support for people who have received the results of genetic testing.
    • Informed consent: Providing patients with complete information about the possibilities and restrictions of genetic testing.

V. Prospects for genetics in the prevention and treatment of diseases:

  1. Personalized medicine:

    • Individual approach: Development of individual prevention and treatment plans based on the genetic data of the patient.
    • Target therapy: The use of drugs aimed at specific genetic mutations in the cells of the body.
    • Pharmacogenetics: The selection of drugs and doses, taking into account the genetic characteristics of the patient.

  2. Gene therapy:

    • Introduction of genes: The introduction of functional genes into the body to compensate for defective genes.
    • Genes editing: Using CRISPR-CAS9 technologies to correct genetic mutations.
    • Treatment of genetic diseases: A promising method of treating many genetic diseases.

  3. Development of new drugs:

    • Identification of targets: The use of genetic data to identify new targets for drugs.
    • Drug development: Creating drugs aimed at these targets.
    • Clinical trials: Conducting clinical tests to assess the effectiveness and safety of new drugs.

  4. Prevention of diseases:

    • Identification of people with high risk: The use of genetic testing to detect people with a high genetic risk of developing diseases.
    • Development of prevention programs: Creation of prevention programs aimed at reducing the risk of developing diseases in people with high genetic risk (for example, changing lifestyle, diet, preventive drugs).

  5. Ethical regulation:

    • Development of norms and rules: Creation of ethical norms and rules governing the use of genetic information.
    • Patient rights protection: Ensuring the protection of patients of patients during genetic testing and the use of genetic information.
    • Enlightenment of society: Information of the company about the possibilities and restrictions of genetics.

VI. Conclusion: The future of genetics in healthcare.

Genetics plays an important role in determining the predisposition to a wide range of diseases. Understanding the influence of genes on human health allows you to develop new methods of prevention, diagnosis and treatment of diseases. The development of genetic technologies opens up new opportunities for personalized medicine and improve the health of the population. It is important to remember the need to comply with ethical norms and rules when using genetic information.

This article provides a detailed and comprehensive overview of the influence of genes on predisposition to diseases. It covers a wide range of topics, from the basics of genetics to specific diseases and methods of studying genetic predisposition. The article also discusses the ethical and social aspects of genetic testing and the future prospects of genetics in healthcare. The structure is organized for readability and SEO optimization.

Leave a Reply

Your email address will not be published. Required fields are marked *