FAQs

Genetic tests look for alterations in a person's genes or changes in the level or structure of key proteins coded for by specific genes. Genetic tests can also be used to look at levels of RNA that play a role in certain conditions. Abnormal results on these tests could mean that someone has a genetic disorder.
Types of genetic tests include:

• Gene tests (individual genes or relatively short lengths of DNA or RNA are tested)
• Chromosomal tests (whole chromosomes or very long lengths of DNA are tested)
• Biochemical tests (protein levels or enzyme activities are tested)

Gene tests look for signs of a disease or disorder in DNA or RNA taken from a person's blood, other body fluids like saliva, or tissues. These tests can look for large changes, such as a gene that has a section missing or added, or small changes, such as a missing, added, or altered chemical base (subunit) within the DNA strand. Gene tests may also detect genes with too many copies, individual genes that are too active, genes that are turned off, or genes that are lost entirely.

Gene tests examine a person's DNA in a variety of ways. Some tests use DNA probes. A probe is a short string of DNA with base sequence complementary to (able to bind with) the sequence of an altered gene. These probes usually have fluorescent tags attached to them. During the test, a probe looks for its complement within a person's genome. If the altered gene is found, the complementary probe binds to it, and the fluorescent label can be used to identify the presence of the alteration.

Another type of gene test relies on DNA or RNA sequencing. This test directly compares the base-by-base sequence of DNA or RNA in a patient's sample to a normal version of the DNA or RNA sequence.

Chromosomes are the large DNA-containing structures in the nucleus of a cell. Humans normally have 23 pairs of chromosomes: 22 pairs of autosomes (numbered 1 through 22) and 1 pair of sex chromosomes (either XX for females or XY for males). Chromosomal tests look at features of a person's chromosomes, including their structure, number and arrangement. These tests look for changes, such as pieces of a chromosome being deleted, expanded, or being switched to a different chromosomal location.

Types of chromosomal tests include:

• Karyotype - This test gives a picture of all of a person's chromosomes from the largest to the smallest. This type of testing can identify changes in chromosome number and large changes in DNA structure. A karyotype would, for instance, identify Down syndrome caused by the presence of an extra copy of chromosome 21
• FISH analysis (fluorescent in situ hybridization) - This test identifies certain regions on chromosomes using fluorescent DNA probes. FISH analysis can find small pieces of chromosomes that are missing or have extra copies. These small changes can be missed by the overall karyotype test.

Biochemical tests look at the amounts or activities of key proteins. Since genes contain the DNA code for making proteins, abnormal amounts or activities of proteins can signal genes that are not working normally. These types of tests are often used for new-born screening. For example, biochemical screening can detect infants who have metabolic conditions such as phenylketonuria (PKU). Because of a genetic defect, people with PKU lack the enzyme that breaks down a particular amino acid (protein building block) called phenylalanine. Consequently, phenylalanine builds up to higher than normal levels in the body, leading to a variety of health problems. If diagnosed early, PKU can be treated with a strict diet that is low in phenylalanine, avoiding foods that are high in protein or that contain certain artificial sweeteners.

Genetic testing can:

1. Give a diagnosis if someone has symptoms.
2. Show whether a person is a carrier for a genetic disease. Carriers have an altered gene, but will not get the disease. However, they can pass the altered gene on to their children.
3. Help expectant parents know whether an unborn child will have a genetic condition. This is called prenatal testing.
4. Screen new born infants for abnormal or missing proteins that can cause disease. This is called new-born screening.
5. Show whether a person has an inherited disposition to a certain disease before symptoms start.

People in families at high risk for a genetic disease have to live with uncertainty about their future and their children's future. A genetic test result that can show that a known alteration causing disease is not present in a person can provide a sense of relief.

A genetic test result showing that a person has a disease-causing gene alteration can also provide benefits. Such a test result might lead a person to take steps to lower his/her chance of developing a disease. For example, as the result of such a finding, someone could be screened earlier and more frequently for the disease and/or could make changes to health habits like diet and exercise. Such a genetic test result can lower a person's feelings of uncertainty, and this information can also help people to make informed choices about their future, such as whether to have a baby.

Diagnostic testing is used to confirm a diagnosis when a person has signs or symptoms that suggest a genetic disease. The particular genetic test used depends on the disease for which a person is tested. For example, if a patient has physical features that suggest Down syndrome, a chromosomal test is used to see if the patient has an extra copy of chromosome 21. To test for Duchenne muscular dystrophy, a gene test is done to look for missing sections in the dystrophin gene.

Predictive testing can show which people have a higher chance of getting a disease before symptoms appear. For example, one type of predictive test screens for inherited genetic risk factors that make it more likely for someone to develop certain cancers, such as colon or breast cancer, or diseases that usually develop later in life, such as adult onset (Type 2) diabetes. Someone with an inherited genetic risk factor may have an increased chance of getting a disease, although this does not mean that the person will certainly get the disease.

Presymptomatic is a type of predictive testing that can indicate which family members are at risk for a certain genetic condition already known to be present in their family. This type of testing is done with people who do not yet show symptoms of that disease. This can be done for Huntington's disease, for example. For some diseases, this type of testing can lead to prevention or treatment options. For example, when a disease-causing alteration for Graves' disease is found in a family, testing is recommended for all close blood relatives (such as parents and siblings). Graves' disease is an autoimmune disease that leads to over-activity of the thyroid gland (hyperthyroidism). Family members with the genetic alteration can be offered treatment, including surgery to remove the thyroid. With other types of diseases, there are no prevention or treatment options. For example, there is no treatment for family members who have a gene alteration causing Huntington's disease. People with this alteration are certain to get the disease.

Preconception/Carrier testing can tell individuals if they have (carry) a gene alteration for a type of inherited disorder called an autosomal recessive disorder. Autosomal means that the altered gene is on one of the 22 chromosomes other than the sex chromosomes (X or Y chromosomes). Recessive means that the person with only one altered copy of the disease gene will not get the disease, but might pass the alteration to their children. If both parents are carriers, their children might inherit an alteration from each parent and get the disease. Examples of autosomal recessive disorders are Thallasemia and Sickle Cell Anaemia

Prenatal testing is available to pregnant women during pregnancy. Some reasons to have genetic testing include:

• Age of the mother. Women age 35 or older are at a higher risk for having a child with chromosomal abnormalities or other birth defects. However, some tests are recommended for all pregnant women, regardless of age.
• A family history of an inherited condition such as Duchenne muscular dystrophy.
• Ancestry or ethnic background indicating that the parents might have a higher chance of carrying an inherited disorder such as sickle cell anemia, common in people of African descent; thalassemia, common in people of Italian, Greek, Middle Eastern, Southern Asian, or African descent; or Tay-Sachs disease, common in people of eastern European (Ashkenazi) Jewish descent.
• To screen for common genetic disorders that may occur during pregnancy, such as Down syndrome or spina bifida. Three diagnostic procedures are common in prenatal testing: ultrasound, amniocentesis, and chorionic villus sampling (CVS). Ultrasound uses the reflection of sound waves to create an overall picture of the developing foetus. Amniocentesis involves testing a sample of amniotic fluid from the womb surrounding the foetus. CVS involves taking a tiny sample of tissue from a region of the placenta that carries foetal cells rather than maternal cells.

Newborn screening is the most widespread type of genetic testing. It is an important public health program that can find disorders in new-borns that might have long-term health effects. New-born screening analyses infant blood samples for abnormal or missing gene products (proteins). For example, infants are often screened for phenylketonuria (PKU), a metabolic disease in which an enzyme deficiency can cause severe mental retardation if the child is not treated. Metabolic disorders are diseases in which gene alterations lead to an inability to break down (metabolize) food and other substances. In the past, new-born screening focused on only a few disorders that lead to mental retardation. Regulations vary from state to state, but all states are now required by law to test for at least 21 disorders, although some states test for 30 or more disorders. These programs now test for disorders that can lead to increased risk of infectious disease, premature death, hearing loss, and heart problems.

People have many different reasons for being tested or not being tested. For many, it is important to know whether a disease can be prevented if a gene alteration causing a disease is found. For example, those who have inherited predispositions to breast or colon cancer have options such as earlier and more frequent disease screening or early treatment.

In other cases, there may be no treatment for the disease. For example are no preventive steps or cures for Huntington's disease but test results might help a person make life decisions, such as career choice, family planning, or insurance coverage.

People can seek advice about genetic testing from a genetic counsellor. Genetic counsellors help individuals and families understand the scientific, emotional, and ethical factors surrounding the decision to have genetic testing and how to deal with the results of those tests.

Genetic professionals work as members of health care teams providing information and support to individuals or families who have genetic disorders or may be at risk for inherited conditions. Genetic professionals:

• Assess the risk of a genetic disorder by researching a family's history, evaluating medical records, and conducting a physical examination of the patient and other family members when indicated.
• Weigh the medical, social and ethical decisions surrounding genetic testing.
• Provide support and information to help a person make a decision about testing.
• Interpret the results of genetic tests and medical data.
• Provide counseling or refer individuals and families to support services.
• Serve as patient advocates.
• Explain possible treatments or preventive measures.
• Discuss reproductive options.

You can find the genetic professional on the following address

Dr. D.K. Chopade
Medical Geneticist
c/o Dr. Deopujari Hospital
Dhantoli, Nagpur
Phone: +91 7122441544 (second Sunday every month)

Genetic Health & Research Center
7, Mahatmanagar, Triambak Road
Nashik, Maharashtra
Phone: +91 253 2350626, +91 9860358501 (all working days)

Your health care provider may refer you to a geneticist - a medical doctor or medical researcher - who specializes in your disease or disorder. A medical geneticist has completed advanced training in medical genetics. While a genetic counsellor may help you with testing decisions and support issues, a medical geneticist will make the actual diagnosis of a disease or condition. Many genetic diseases are so rare that only a geneticist can provide the most complete and current information about your condition.

Along with a medical geneticist, you may also be referred to a physician who is a specialist in the type of disorder you have.

A genetic disorder is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence. Genetic disorders can be caused by a mutation in one gene (monogenic disorder), by mutations in multiple genes (multifactorial inheritance disorder), by a combination of gene mutations and environmental factors, or by damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes).

As we unlock the secrets of the human genome (the complete set of human genes), we are learning that nearly all diseases have a genetic component. Some diseases are caused by mutations that are inherited from the parents and are present in an individual at birth, like sickle cell disease. Other diseases are caused by acquired mutations in a gene or group of genes that occur during a person's life. Such mutations are not inherited from a parent, but occur either randomly or due to some environmental exposure (such as cigarette smoke). These include many cancers, as well as some forms of neurofibromatosis.

Genetic disorders typically involve the inheritance of a particular mutated disease-causing gene, such as sickle cell disease, cystic fibrosis, and Tay-Sachs disease. The mutated gene is passed down through a family, and each generation of children can inherit the gene that causes the disease. Rarely, one of these monogenic diseases can occur spontaneously in a child when his/her parents do not have the disease gene, or there is no history of the disease in the family. This can result from a new mutation occurring in the egg or sperm that gave rise to that child.

Most genetic disorders, however, are "multifactorial inheritance disorders," meaning they are caused by a combination of inherited mutations in multiple genes, often acting together with environmental factors. Examples of such diseases include many commonly-occurring diseases, such as heart disease and diabetes, which are present in many people in different populations around the world.

Research on the human genome has shown that although many commonly occurring diseases are usually caused by inheritance of mutations in multiple genes at once, such common diseases can also be caused by rare hereditary mutations in a single gene. In these cases, gene mutations that cause or strongly predispose a person to these diseases run in a family, and can significantly increase each family member's risk of developing the disease. One example is breast cancer, where inheritance of a mutated BRCA1 or BRCA2 gene confers significant risk of developing the disease. .

Monogenetic disorders are caused by a mutation in a single gene. The mutation may be present on one or both chromosomes (one chromosome inherited from each parent). Examples of monogenic disorders are: sickle cell disease, cystic fibrosis, polycystic kidney disease, and Tay-Sachs disease. Monogenic disorders are relatively rare in comparison with more commonly-occurring diseases, such as diabetes and heart disease. A major distinction among monogenic disorders is between "dominant" and "recessive" diseases. Dominant diseases are caused by the presence of the disease gene on just one of the two inherited parental chromosomes. In dominant diseases, the chance of a child inheriting the disease is 50 percent. In a family situation, for example, if the parents have four children, it may be possible that two of those children inherit the disease gene. Examples of dominant diseases are Huntington's disease and Marfan syndrome. Recessive diseases require the presence of the disease gene on both of the inherited parental chromosomes. In this case, the chance of a child inheriting a recessive disease is 25 percent. In the family example, if the parents have four children, it may be more likely that only one child will develop the disease. Examples of recessive diseases include cystic fibrosis and Tay-Sachs disease.

Multifactorial inheritance disorders are caused by a combination of small inherited variations in genes, often acting together with environmental factors. Heart disease, diabetes, and most cancers are examples of such disorders. Behaviours are also multifactorial, involving multiple genes that are affected by a variety of other factors. Researchers are learning more about the genetic contribution to behavioural disorders such as alcoholism, obesity, mental illness and Alzheimer's disease.

Chromosome disorders are caused by an excess or deficiency of the genes that are located on chromosomes, or by structural changes within chromosomes. (See the NHGRI fact sheet about chromosome abnormalities; Down syndrome, for example, is caused by an extra copy of chromosome 21 (called trisomy 21), although no individual gene on the chromosome is abnormal. Prader-Willi syndrome, on the other hand, is caused by the absence or non-expression of a group of genes on chromosome 15. A specific form of blood cancer (chronic myeloid leukemia, CML) may be caused by a chromosomal translocation, in which portions of two chromosomes (chromosomes 9 and 22) are exchanged. No chromosomal material is gained or lost, but a new, abnormal gene is formed that leads to formation of cancer.