Genetic testing: Everything you need to know

As per the Organization of Rare diseases in India (ORDI), 1 in 20 Indians is affected by a rare disorder. More than 7,000 rare diseases are known and reported worldwide; from these approximately 80 per cent are known to have a genetic predisposition. Some of these “common” rare diseases we’ve heard of are inherited cancers (eg. breast, ovarian, and colorectal etc.), hemoglobinopathies (hemophilia, thalassemia, and sickle cell anemia etc.), auto-immune deficiencies, and lysosomal storage disorders among others, says Dr Aparna Dhar, head of department: medical genetics and genetic counselling, CŌRE Diagnostics.

“In the year 2020, the world has undergone massive changes. It has made us introspect and re-evaluate our lives. We’ve started looking after our wellbeing by addressing issues associated with mental health and physical health. We’ve consciously tried to bring about lifestyle changes that have been coupled with teaming up with healthcare/diagnostic providers to give us a more personalised approach. One key way of doing this is by understanding if they have a genetic pre-disposition to a hereditary disorder,” she adds.

A global study conducted by the Mayo Clinic, USA stated that 1 in 10 people who underwent predictive genetic testing, learned that they had a hereditary risk for a health condition and could actually benefit from preventive care. While no genetic test can accurately predict the exact date and time a disease may present, it will definitely be able to tell if an individual is at a higher risk vs the general population risk.

However, Dr Dhar says that there is definitely a lack of awareness around these genetic disorders, misconception about genetic diseases and testing, taboo talking about a potential familial disorder, and cost challenges.

Below, she addresses some of these:

What is a genetic test?

Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. More than 1,000 genetic tests are currently in use, and more are being developed. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue.

For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person’s doctor or genetic counselor, or directly to the patient if requested.

How should one prepare for genetic testing?

Genetic testing can provide important, life-saving information. Interpreting the results is critical. It can be difficult for a medical doctor to understand the result if they don’t have specialized training in genetics. That’s why genetic counselors exist. They are trained in both medical genetics and counseling and work closely with your doctor to provide both clinical and emotional advice. They are available to guide, to make sure if you are a good fit for the test and help interpret results. Whereas for some, they might have second thoughts and might not recommend genetic testing as it is not for everyone. While there is perceived stigma of resulting to some disease or bad gene still lies, a counselor will help you understand what the results mean for you and your family.

What useful information can genetic testing provide?

*Genetic testing can provide clarity on the results, guide therapy selection and monitoring, and allow disease risk profiling
*Family health history tells you which diseases run in your family
*Identify risks due to shared genes
*Understand better what lifestyle and environmental factors you share with your family
*Understand how healthy lifestyle choices can reduce your risk of developing a disease

The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done.

A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicating that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or pre-symptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition.

A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result.

In some cases, a test result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result.

Path to well-being

Genetic testing is not limited to only helping from a preventive and proactive perspective, but for those affected with disease; there is a shift to personalised medicine paradigm of disease modeling and targeted gene therapy which has yielded excellent results. In addition, the data from the Human Genome Project has helped us understand the stratification of genes as per their penetrance levels and in turn, help us give a personalised risk assessment to our patients.