Genetic Testing: Genetic carrier, Oncogenes, Drug allergy genes

Choose the content to read

• Why genetic testing?
• What diseases can genetic testing detect?
• What is the genetic testing procedure?
• What does the genetic testing result mean?
• What are the benefits of genetic testing?
• Genetic Testing at MedPark Hospital

Genetic Testing

Genetic testing, or genomic testing, is a medical test that looks for genetic variants or mutated genes in DNA to identify a genetic carrier, assess the risk of genetic disorders, and prevent genetic disease transmission to children. Genetic testing aids in the detection of genetic mutations caused by genetic variations derived from parents to children, such as thalassemia carrier genes, oncogenes, drug allergy genes, or cardiovascular disease genes, allowing medical geneticists to diagnose genetic disorders, rare diseases, or incurable chronic illnesses effectively. Genetic testing can also help predict disease onset, plan accurate and appropriate treatment, and provide guidance for long-term health care.

Why genetic testing?

There are over 7,000 different types of genetic-based disorders and rare diseases. Common genetic disorders, including thalassemia, congenital hearing loss, and congenital hypothyroidism, cause babies born with poor health to be at high risk of complications and necessitate lifelong treatment. Genetic testing uses the expanded carrier screening (ECS) procedure to screen for genetic disease carriers caused by a single gene, aids in disease prediction and helps assess the risk of passing certain genetic disorders down to children.

For young adults with early-onset, hereditary cancers, those with multiple family members who have had cancer, those with various types of cancer or multiple locations of cancer, even if they do not occur at the same time, and those who have cancer in two regions at the same time, such as breast cancer on both sides of the breast, genetic testing aids in the detection of oncogenes and increases the chances of a cure if the cancer is detected early.

For those with epilepsy, gout, tuberculosis, or HIV, taking anti-seizure medications for these conditions can cause serious side effects, such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), which can be life-threatening. Pharmacogenomics testing assists medical geneticists in selecting and managing the appropriate dosage of drugs for safety, preventing adverse drug reactions, reducing allergic reactions, and decreasing mortality rates.

How many types of genetic testing?

There are many types of genetic testing, or genomic testing. Medical geneticists will consider the most appropriate test based on each individual's conditions and needs. The most common genetic tests available today include the following:

1. Newborn screening is screening for diseases or groups of diseases that cause intellectual disability, disability, or death, including inherited metabolic disorders, congenital hypothyroidism, or phenylketonuria. Newborn screening enables doctors to plan treatment in advance, reducing the disease's symptoms and severity. For example, if a doctor suspects abnormal metabolites, they may order a blood chemistry test, followed by a confirmatory test with genetic testing to confirm the diagnosis.
2. Carrier testing looks for genetic carrier genes such as thalassemia, sickle cell disease, or muscular dystrophy (MD). Carrier testing identifies latent genes or carriers before deciding to have children, lowering the risk of passing on genetic diseases to children and determining alternative treatment options for having children, such as IVF or ICSI.
3. Predictive and presymptomatic testing looks for mutated genes or latent disease-causing genes before disease symptoms appear in the future, which is certain to occur but cannot be predicted when, particularly for those with a family history of a disease such as familial colorectal cancer, breast cancer, pancreatic cancer, hypertrophic cardiomyopathy, heart arrhythmia, sudden cardiac arrest, or hereditary neurological conditions such as Huntington's disease.
4. Pharmacogenetics testing looks for genetic variants associated with drug hypersensitivity reactions or altered metabolisms to reduce the risk of serious side effects from drug-induced hypersensitivity reactions, which can be life-threatening, particularly for those with epilepsy, gout, tuberculosis, or HIV, and to adjust the dosage and manage drug usage appropriately to effectively fight those diseases or symptoms safely.
5. Preimplantation testing is the screening of embryo chromosomes derived from the in vitro fertilization (IVF/ICSI) procedure prior to transferring the embryo back into the uterus to achieve a successful pregnancy outcome and conceive a healthy baby free of genetic diseases such as Down syndrome, Edwards syndrome, or Turner syndrome. Preimplantation testing can also help couples with infertility conceive successfully.

What diseases can genetic testing detect?

Genetic testing can detect numerous genetic disorders or abnormalities, including the following:

• Down syndrome
• Thalassemia
• Congenital hearing loss
• Inherited metabolic disorders
• Colorectal cancer
• Breast cancer
• Pancreatic cancer
• Hypertrophic cardiomyopathy
• Heart arrhythmia
• Sudden cardiac arrest
• Autoinflammatory diseases

Who should get genetic testing?

• Those with familial hereditary cancer, cardiovascular disease, rare diseases, or genetic disorders.
• Those who have had multiple cancers, either synchronous or asynchronous.
• Carriers who carry mutated genes and wish to start a family and have healthy children.
• Those who experience recurrent sickness or an unexplained chronic illness.
• Parents who have had children with genetic disorders such as Down syndrome, sickle-cell anemia, or thalassemia.

What is the genetic testing procedure?

1. Genes Collecting
   The medical geneticist will collect tissue samples to look for genetic variants, changes, or mutations using various sources such as blood, saliva, hair, skin, tissue, buccal mucosa, or amniocentesis.
2. DNA Sequencing
   The medical geneticist will send the collected sample to a genomic laboratory to test for mutated genes or genetic variants at the DNA level using Next Generation Sequencing (NGS) technology to aid in fast and accurate testing results through the following genetic testing procedures:
   • Targeted Variant Testing to identify genetic variants associated with rare diseases, particularly in exon genome regions such as the deletion of the SMN1 gene that causes muscular dystrophy (MD), or to look for genes associated with drug-induced hypersensitivity reactions such as the HLA-B*5801 gene to prevent the onset of drug allergy rashes related to SJS or TEN in those with gout before prescribing allopurinol or the HLA-B*1502 gene in those with epilepsy before prescribing an antiepileptic medication, i.e. carbamazepine.
   • Multi-Genes Panel Sequencing looks for genetic variants in a group of pre-selected genes, such as the BRCA1 and BRCA2 genes to determine the risk of hereditary breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, or prostate cancer, and the MYBPC3 and MYH7 genes to determine the risk of cardiovascular disease.
   • Whole Exome Sequencing (WES) In cases where there is no readily identifiable disease or syndromic group, doctors may consider whole exome sequencing (WES) to identify some genetic variants associated with rare diseases, particularly in exon genome regions, even though they account for only 1.5–2% of the total genomic DNA. WES testing in each exon enables doctors to identify causative gene variants, which account for up to 80% of disease cases.
   • Whole Genome Sequencing (WGS) is a DNA sequencing test that looks for the genetic makeup of 3 billion base pairs at once in order to decode the entire body's genetic material and detect genetic mutations that cause genetic disorders, rare diseases, or unexplained sickness, particularly if the causative variant is not located in the exons. WGS testing to examine the entire genomic DNA sequence can aid in the identification of the causal variant.
3. DNA Analyzing
   The computer system processes data using the massive parallel sequencing (MPS) of overlapping DNA molecules to read a large number of genetic sequences simultaneously while synthesizing genetic material. The collected data is then fed into bioinformatics systems to reconstruct DNA molecules and identify genetic variants that cause genetic diseases.
4. Results Reporting
   When the genetic testing procedure is complete, the genomic laboratory will send the results, which include gene details, to the medical geneticist, who will summarize and inform the examinee of the genetic testing results and provide a personalized treatment plan, prevention instructions, and appropriate healthcare guidance suitable for the examinee’s condition.

What does the genetic testing result mean?

The genetic testing results can be reported into 3 types:

1. Positive result
   The genetic testing results indicate changes in one or more genes, either carrier genes or mutated genes. The examinee is at a high risk of developing a genetic disorder or passing down genetic diseases to their offspring. A positive result indicates the status of the latent carrier genes in the body, aids in identifying the cause of the illness, and alerts other family members to have genetic testing to look for carrier genes and risk status.
2. Negative result
   The genetic testing result indicates no changes in genes, no carrier genes, or no mutated genes. The examinee is not at risk of developing a genetic disorder or passing on genetic diseases to their offspring. However, the absence of mutated genes does not confirm that they will not develop a genetic disease in the future. Therefore, the medical geneticist recommends annual health checkups. 
3. Variant of uncertain significance (VUS) 
   The genetic testing result indicates changes in one or more genes, either carrier genes or mutated genes. However, it is too early to predict whether the mutated gene is a disease-causing gene or a normal gene with natural genetic variation. For those who have variants of uncertain significance test results, the medical geneticist will order additional specific tests to obtain a conclusive outcome. This is because, in the long run, inconclusive test results can possibly change the test result to either positive or negative.

How long does it take for the genetic testing result?

Typically, single gene or small gene panel testing results are available within 2-4 weeks, whereas WES, WGS, or other complex genetic testing may require an additional 1-2 months to process and interpret the results.

How accurate is genetic testing?

Genetic testing can detect the presence of a carrier gene, a mutated gene, or a gene with an abnormal genetic variant at high accuracy, even though the test result is not 100% certain. However, for those with familial hereditary cancers, rare diseases, or unexplained illnesses, genetic testing can help identify the mutated gene that causes genetic disorders, leading to appropriate treatment and plans for long-term health maintenance.

What are the benefits of genetic testing?

• Inform crucial health information: Typically, 5% of the population suffers from one or more rare diseases. Genetic testing can help detect genetic variants or mutated genes that cause rare diseases, including oncogenes or tumor suppressor genes, inform crucial health information, and guide appropriate healthcare guidance.
• Risk assessment: Genetic testing assesses the risk of developing a genetic disease and guides medical decisions about receiving appropriate treatment to lower the risk. For example, for women with a family history of mothers, sisters, grandmothers, or great-grandmothers having breast cancer or ovarian cancer, the detection of a genetic mutation in the BRCA1 or BRCA2 gene can help guide the decision of whether to have a prophylactic mastectomy or oophorectomy to decrease the risk of breast cancer or ovarian cancer.
• Advance treatment planning: Genetic testing helps identify and explain the cause of abnormalities, allowing the doctor to plan appropriate treatment in advance. For example, in children with autism or developmental delays, detecting a genetic mutation in the FMR1 gene assists parents in finding out the cause of the behaviors and enables the child to receive early treatment.
• Provide precision treatment: Those who carry genetic variants associated with drug hypersensitivity reactions are 55 times more likely to develop SJS or TEN than those who do not. Detecting HLA-B*1502 gene mutations can reduce the risk of drug allergy rashes, enable medical geneticists to prescribe the appropriate medications, and significantly lower treatment costs.
• Proactive disease prevention: Genetic testing promotes proactive healthcare. For those with a family history of cardiovascular disease, the polygenetic risk score (PRS) test helps identify the risk of cardiovascular disease such as coronary artery disease or atrial fibrillation. This promotes lifestyle and behavioral changes such as exercising regularly in order to lose weight, avoiding high-fat foods, abstaining from alcohol and smoking, getting enough rest, and avoiding stress.
• Preventive medicine: Genetic testing is a preventive medicine that may help detect genetic variants that increase the risk of future cancer, leading to appropriate cancer screening plans based on individual risks, such as the age at which cancer screening should begin, the appropriate screening method, and the frequency of screening.

Genetic Testing at MedPark Hospital

Genomics Medicine Center, MedPark Hospital, Bangkok, Thailand, is led by a team of medical geneticists with extensive experience in genetic testing, DNA sequencing of genetic disorders, rare diseases, and chromosomal abnormalities, in close collaborative work with a team of geneticists in the ISO-certified clinical laboratories to provide genetic testing and interpret complex genetic sequences using state-of-the-art Next Generation Sequencing (NGS) technology, enabling accurate, rapid, and precise test results, leading to accurate, prompt, and effective treatment planning, integrating with a team of pharmacists who specialize in pharmacogenomics to help manage the dosage of medications as prescribed by the medical geneticists to meet the needs of each patient, preventing allergic reactions, reducing complications, and allowing patients to have a good quality of life, as well as a healthy physical, and a chance of curable.