Genetic tests: opportunities and restrictions on health assessment
1. Fundamentals of genetic testing
Genetic tests analyze human DNA to identify changes or mutations in genes, chromosomes or proteins. These changes may indicate an increased risk of developing certain diseases, the probability of transmitting genetic diseases to the offspring or a predisposition to certain characteristics. The development of DNA sequencing technologies in recent decades has significantly expanded the possibilities of genetic testing, making it more accessible and accurate.
1.1. What are DNA and genes?
Deoxyribonucleic acid (DNA) is a molecule containing genetic instructions necessary for the development, functioning and reproduction of all known living organisms and many viruses. DNA consists of two interconnected chains twisted into a spiral, forming a double spiral. Each chain consists of a sequence of nucleotides consisting of deoxyribose sugar, phosphate group and one of the four nitrogenous bases: adenine (a), guanine (G), cytosine (C) and Timin (t). The sequence of these bases determines the genetic code.
Genes are DNA areas that contain instructions for the synthesis of proteins or functional RNA molecules. Proteins perform a wide range of functions in the body, from catalysis of biochemical reactions to the formation of structural components of cells and tissues. Each gene has a certain location (locus) on the chromosome.
1.2. Types of genetic tests
There are several types of genetic tests designed to identify various types of genetic changes:
- Diagnostic testing: It is used to confirm or exclude the diagnosis of a genetic disease in a person with symptoms. For example, diagnostic testing can be carried out to confirm the diagnosis of cystic fibrosis in a child with respiratory problems and an increased level of chloride in sweat.
- Predictive testing: It is used to assess the risk of developing a genetic disease in the future in a person without symptoms. For example, prognostic testing can be carried out to assess the risk of developing Huntington’s disease in a person whose parent suffers from this disease.
- Screening testing: It is used to identify genetic diseases or predisposition to them in a certain population. For example, the screening of newborns is carried out to identify several genetic diseases that can be successfully treated if they are diagnosed at an early stage.
- Prenatal testing: It is carried out during pregnancy to assess the risk of genetic diseases in the fetus. For example, prenatal testing can be carried out to detect Down syndrome.
- Preimplantation genetic testing (PGT): It is carried out on embryos created in the process of in vitro fertilization (IVF) to identify genetic defects before implantation into the uterus.
- Pharmacogenetic testing: It is used to determine how a person will respond to certain drugs based on his genetic profile. This helps doctors choose the most effective and safe drugs and dosage for each patient.
- Narrow testing: It is used to determine whether a person is a carrier of a genetic disease. Harshes usually do not have symptoms, but can convey the gene to their children.
- The genealogy examination (establishment of paternity/motherhood): Comparison of genetic markers to establish biological kinship.
1.3. Genetic testing methods
There are many methods used for genetic testing, each of which has its own advantages and restrictions:
- DNA sequencing: Determination of the exact sequence of nucleotides in the gene or genome. DNA sequencing is the most accurate and informative method of genetic testing, but also the most expensive. There are various sequencing methods, including Senger sequencing (traditional method) and sequencing of a new generation (NGS), which allows you to simultaneously secure many genes or the entire genome.
- Polymerase chain reaction (PCR): The method used for amplification (copying) of a certain DNA section. PCR is used to increase the amount of DNA so that it can be easily analyzed.
- Fluorescence hybridization in situ (fish): A method used to visualize certain DNA sections on chromosomes. Fish is used to identify chromosomal abnormalities, such as deletions, duplication and translocation.
- Chromosomal micrust analysis (CMA): The method used to identify changes in the amount of DNA in the genome. CMA is used to detect deletions and duplications that can be associated with genetic diseases.
- Analysis single -nucleotide polymorphism (SNP): The method used to identify variations in the DNA sequence, which are often found in the population. SNP can be associated with the risk of developing certain diseases or a reaction to drugs.
- Printing citometry: The method used to analyze cells based on their physical and chemical characteristics. Propromic citometry can be used to detect abnormal cells, such as cancer cells.
2. The possibilities of genetic testing in the assessment of health
Genetic testing provides wide opportunities for assessing health and making informed decisions on the prevention, diagnosis and treatment of diseases.
2.1. Diagnosis of genetic diseases
Genetic testing plays a key role in the diagnosis of genetic diseases, especially those that are difficult to diagnose based on clinical symptoms. Early and accurate diagnosis of genetic diseases can allow treatment and improve the prognosis in a timely manner. Examples of genetic diseases diagnosed using genetic testing include:
- MukoviScidoz: A genetic disease that affects the lungs, pancreas and other organs. Genetic testing allows you to identify mutations in the CFTR gene that cause cystic fibrosis.
- Huntington disease: A neurodegenerative disease, causing a progressive deterioration in motor, cognitive and psychiatric functions. Genetic testing allows you to reveal an increase in the number of trinucleotide reckonings of CAG in the HTT gene, which is the cause of Huntington’s disease.
- Sickle -cell anemia: A genetic blood disease in which red blood cells have an abnormal shape, which leads to impaired blood flow and anemia. Genetic testing allows you to identify mutations in the HBB gene, which cause sickle cell anemia.
- Down syndrome: Chromosomal disease caused by the presence of an additional copy of the 21st chromosome. Prenatal genetic testing, such as amniocentesis or chorion biopsy, can detect Down syndrome in the fetus.
- Spinal muscle atrophy (SMA): A genetic disease affecting motor neurons, which leads to progressive muscle weakness and atrophy. Genetic testing allows you to identify deletions or mutations in the SMN1 gene, which cause SMA.
2.2. Risk assessment of diseases
Genetic testing can be used to assess the risk of various diseases, including cancer, cardiovascular diseases, diabetes and neurodegenerative diseases. The identification of a genetic predisposition to certain diseases allows you to take preventive measures, such as a change in lifestyle, regular medical examinations and preventive treatment, in order to reduce the risk of the development of the disease or to identify it at an early stage, when treatment is most effective. Examples of genetic tests used to assess the risk of developing diseases include:
- Testing on mutations of genes BRCA1 and BRCA2: These genes are involved in the restoration of DNA, and mutations in these genes increase the risk of developing breast cancer, ovarian cancer and other types of cancer.
- Testing for genetic options associated with Alzheimer’s disease: Some genetic options, such as APOE4, increase the risk of developing Alzheimer’s disease.
- Testing for genetic options associated with cardiovascular diseases: Some genetic options, such as LPA, increase the risk of developing cardiovascular diseases.
- Testing for genetic options associated with type 2 diabetes: Some genetic options increase the risk of type 2 diabetes.
2.3. Pharmacogenetics: a personalized approach to treatment
Pharmacogenetic testing allows you to determine how the human genetic profile affects his reaction to certain drugs. This information can be used to select the most effective and safe drugs and dosages for each patient, which avoids side effects and increase the effectiveness of treatment. Examples of the use of pharmacogenetic testing include:
- Varfarin: Anticoagulant used to prevent blood clots. Pharmacogenetic testing of CYP2C9 and VKORC1 genes helps to determine the optimal dose of warfarin for each patient to avoid bleeding or insufficient anticoagulation.
- Clopidogrel: The anti -cargant used to prevent the formation of blood clots after a heart attack or stroke. Pharmacogenetic testing of the CYP2C19 gene helps to determine whether the patient will effectively respond to clopidogrel.
- Antidepressants: Pharmacogenetic testing of genes involved in the metabolism of antidepressants can help doctors choose the most effective antidepressant and a dose for each patient.
- Oncological drugs: Pharmacogenetic testing can help determine whether the patient will respond to certain oncological drugs and what side effects can be expected.
2.4. Reproductive planning and prenatal diagnostics
Genetic testing plays an important role in reproductive planning and prenatal diagnosis. Testing for carriage allows you to identify pairs that are carriers of genes associated with genetic diseases, and evaluate the risk of a child with such a disease. Prenatal genetic testing allows you to identify genetic diseases in the fetus during pregnancy. Examples of the application of genetic testing in reproductive planning and prenatal diagnosis include:
- Testing for the carriage of cystic fibrosis, spinal muscle atrophy and other genetic diseases: Paps planning pregnancy can undergo carriage testing to evaluate the risk of a child with these diseases.
- Preimplantation genetic testing (PGT): Embrions created in the process of IVF can be tested on genetic defects before implantation in the uterus.
- Non -invasive prenatal testing (nipt): Analysis of DNA of the fetus circulating in the blood of the mother to detect chromosomal abnormalities, such as Down syndrome.
- Amniocentesis and biopsy chorion: Invasive methods of prenatal diagnosis in which samples of amniotic fluid or chorion tissue are taken for the genetic analysis of the fetus.
2.5. Screening of newborns
Screening of newborns is a program aimed at identifying certain genetic diseases in newborns, which can be successfully treated if they are diagnosed at an early stage. Early diagnosis and treatment of these diseases can prevent serious complications and improve the quality of life of the child. Examples of diseases detected by screening of newborns include:
- Phenylketonuria (FCU): A genetic disease in which the body cannot split the phenylalanine amino acid. Early diagnosis and low -content diet can prevent mental retardation.
- Congenital hypothyroidism: A condition in which the thyroid gland does not produce enough hormones of the thyroid gland. Early diagnosis and treatment with thyroid hormones can prevent developmental delay.
- Galactosemia: A genetic disease in which the body cannot split galactose sugar. Early diagnosis and diet without galactose can prevent damage to the liver, kidneys and brain.
- MukoviScidoz: Early diagnosis and treatment can improve the prognosis for children with cystic fibrosis.
3. Limitations of genetic testing in health assessment
Despite numerous opportunities, genetic testing has a number of restrictions that must be taken into account when interpreting the results and making health decisions.
3.1. Incomplete penetrance and variable expressiveness
- Incomplete penetrance: It means that not all people who have a certain genetic version will develop the disease associated with it. For example, some people with a mutation in the BRCA1 gene may never get breast cancer or ovarian cancer.
- Various expressiveness: It means that in people who have a certain genetic version and develop the disease associated with it, the symptoms and severity of the disease can vary. For example, in people with Huntington’s disease, the age of the beginning and the rate of progression of the disease can vary.
These phenomena are due to the influence of other genes, environmental factors and random events that can modulate the expression of genes and the development of diseases. Therefore, the presence of a genetic variant associated with the disease does not always mean that a person will definitely get this disease, and even if he gets sick, then the severity and course of the disease can not always be predicted.
3.2. Genetic heterogeneity
Genetic heterogeneity means that the same disease can be caused by mutations in different genes. For example, cystic fibrosis can be caused by mutations in the CFTR gene, but there are more than 2000 different mutations in this gene that can cause cystic fibrosis. In addition, some cases of cystic fibrosis can be caused by mutations in other genes that affect CFTR protein function.
Genetic heterogeneity complicates the diagnosis of genetic diseases, since it is necessary to test many genes and mutations in order to determine the cause of the disease. In addition, genetic heterogeneity can affect the prognosis and treatment of the disease, since different mutations can lead to different severity and course of the disease.
3.3. Ethnic and population specificity
The frequency of certain genetic options can vary in different ethnic groups and populations. For example, mutations in the BRCA1 gene, which are often found in people of European origin, can be less common in people of African or Asian origin. Therefore, the interpretation of the results of genetic testing should take into account the ethnic origin of the patient.
In addition, genetic tests developed and validated for one population can be less accurate or informative for another population. Therefore, it is important to use genetic tests that were developed and validated for the population to which the patient belongs.
3.4. Limited database of genetic options
The databases of genetic options used to interpret the results of genetic testing are constantly replenished, but still incomplete. This means that some genetic options detected by genetic testing may not be well studied, and their effect on health may be unknown.
In such cases, the genetic version is classified as “variant of indefinite significance” (VUS). VUS means that information is not enough to determine whether the genetic version is pathogenic (causing a disease) or benign (not affecting health). VUS can cause concern in patients and doctors, since they do not provide clear information about the risk of the disease.
3.5. Psychological and social consequences
Genetic testing can have significant psychological and social consequences for patients and their families. The results of genetic testing can cause anxiety, depression, guilt and stigmatization. For example, people who have revealed a genetic predisposition to cancer may experience increased anxiety and fear of cancer.
In addition, the results of genetic testing can affect relations with family and friends. For example, people who are carriers of a genetic disease may experience guilt in front of their children or other family members who can inherit the disease.
It is important that patients receive consultations from genetic consultants before and after genetic testing, so that they can understand the test results and cope with the psychological and social consequences.
3.6. Ethical questions
Genetic testing raises a number of ethical issues, including confidentiality, justice and discrimination.
- Confidentiality: The results of genetic testing are personal information, which must be protected from unauthorized access. Insurance companies and employers can use the results of genetic testing to discriminate people with a genetic predisposition to diseases.
- Justice: Genetic testing should be available to everyone who needs it, regardless of their socio-economic status. Currently, genetic testing is often expensive and inaccessible to many people.
- Discrimination: Laws should protect people from discrimination based on their genetic information. In some countries, there are laws prohibiting insurance companies and employers to use genetic information to make decisions.
4. Interpretation of genetic testing results
The interpretation of the results of genetic testing is a difficult task that requires knowledge in the field of genetics, medicine and statistics. The results of genetic testing should be interpreted in the context of the patient’s personal and family health history, as well as taking into account the ethnic origin of the patient and available databases of genetic options.
4.1. The role of genetic counseling
Genetic counseling plays an important role in the process of genetic testing. Genetic consultants are specialists who have training in the field of genetics and counseling. They help patients understand the possibilities and limitations of genetic testing, interpret the results of tests and make informed health decisions.
Genetic consultants can help patients:
- Determine whether genetic testing is suitable for them.
- Choose a suitable genetic test.
- Understand the results of a genetic test.
- Assess the risk of developing the disease based on the test results.
- Develop a plan for the prevention and treatment of the disease.
- Cope with the psychological and social consequences of genetic testing.
4.2. Factors affecting the interpretation of the results
Several factors can affect the interpretation of genetic testing results:
- Penetrance and expressiveness: As mentioned earlier, penetrance and expressiveness can affect the likelihood of developing a disease in a person with a certain genetic version.
- Genetic heterogeneity: Genetic heterogeneity complicates the determination of the cause of the disease, since it is necessary to test many genes and mutations.
- Ethnic and popular specifics: The frequency of certain genetic options can vary in different ethnic groups and populations.
- Limited database of genetic options: Some genetic options may not be well studied, and their effect on health may be unknown.
- Family History: Family history of health can help determine the likelihood that a certain genetic version is pathogenic.
5. Future of genetic testing
Genetic testing continues to develop rapidly, and in the future new opportunities and application are expected.
5.1. Development of new generation security technologies (NGS)
NGS technologies are becoming more accessible and economically effective, which allows wider and deeper genetic testing. In the future, NGS can be a standard method of genetic testing for many diseases.
5.2. Genomic editing (CRISPR)
CRISPR technology allows you to accurately edit genes in cells and organisms. In the future, CRISPR can be used to treat genetic diseases by correcting mutations in genes.
5.3. Artificial intelligence (AI) in genetics
AI is used to analyze the large volumes of genetic data, the identification of new genetic options related to diseases, and the development of new methods of diagnosis and treatment of genetic diseases. In the future, AI can revolutionize genetics and personalized medicine.
5.4. Expansion of the screening of newborns
The screening of newborns can be expanded to include more genetic diseases that can be successfully treated if they are diagnosed at an early stage.
5.5. Personalized medicine
Genetic testing will become an increasingly important component of personalized medicine, allowing doctors to develop individual plans for the prevention and treatment of diseases based on the genetic profile of each patient.
6. Conclusion (as indicated in the task, the conclusion is not included)