SCIENCE

What is a gene?

Genes are the parts of our genetic information, called DNA, that contain the information needed for a cell to make proteins. These instructions are in the form of a code using four types of molecules called nucleotides: Adenine (A), Thymine (T), Guanine (G) and Cytosine (C). Depending on the order in which these molecules are arranged, different proteins can be produced by different genes.

How do genes work?

All human beings have nearly the same set of about 20,000 genes. These are present in our DNA in almost every single cell in our bodies. The specific sequence of As, Ts, Cs and Gs that make up each gene can be "read" by a cell and "translated" into the corresponding protein.

Proteins produced from these genes perform almost all the functions of our body — they build muscles, skin, bones and all organs; they maintain the shape and structure of different cells; they digest nutrients and deliver molecules to different destinations.

What are mutations?

Sometimes the DNA can carry a “mistake” in it, resulting in a change of the sequence of the gene. Such sequence changes are also named as “variants”.

Some examples of these changes include:

• Replacement of one part of the sequence with another (like a spelling error)
• An insertion/deletion of a small or large part of the sequence

Some of these changes are harmless (benign) while others can cause disease and are called mutations.

How do we get mutations?

Most mutations are inherited from one or both parents. However, sometimes a mutation can arise spontaneously (de novo) or due to exposure to external factors in developing embryo or fetus.

Why are mutations dangerous?

Mutations in a gene can change the instructions to make the protein. This can lead to the gene not producing any protein at all; to produce a defective protein that cannot perform its functions in the cell; or to produce a protein that harms other proteins.

What are genetic diseases?

It is one of the scenarios above, where the protein is not performing its intended function, that can cause genetic disease. Depending on the function of the missing or abnormal protein, the individual carrying the mutation can be affected in different parts of the body and develops the symptoms of the disease.

To date about 5,600 single gene disorders have been identified.

Why are mutations hereditary?

An individual carries two copies of each gene, one inherited from each biological parent. Exceptions are genes in certain regions of the sex chromosome.

Both copies may be healthy, or one may be healthy while the other may carry a mutation, or both may carry mutations. If the person carries a mutation in at least one of their gene copies, then they can pass on that mutation to their offspring.

In this manner, genetic mutations can be inherited and passed down from generation to generation.

If a mutation is passed down, will it always cause disease?

Not always. This depends on the gene with the mutation.

For some genes, both copies of the gene (the one inherited from the mother and the one inherited from the father) should have a mutation causing both copies of the gene to be non-working. So if the individual inherits one mutated copy of the gene but the second copy is working, they do have disease. However, they are a carrier for a mutation and can pass on the mutation to the next generation. Diseases inherited in this manner are referred to as autosomal recessive diseases.

For some genes, a mutation when present in only one of the two gene copies can already cause a disease in the individual. Having a normal second copy does not offer any protection for these diseases. So if an individual inherits a mutation from a parent who is affected, then the individual is also likely to be affected themselves. Diseases inherited in this manner are referred to as autosomal dominant diseases.

When the mutation is present in a gene located in certain regions of the X-chromosome, men are more frequently affected than women. This is because unlike the other 22 pairs of chromosomes, sex chromosomes in men are not completely paired. Men have one X-chromosome and one Y-chromosome and some of the genes have a copy of both chromosomes. When men inherit a mutation in a gene that is only present in their X-chromosome without a copy of the Y-chromosome, their only copy of this gene is non-working. Therefore, they are affected with the disease. Women, on the other hand, have two X-chromosomes. That means they have a high chance of being “protected” by a second working copy of the gene. Diseases inherited in this manner are called X-linked diseases.

What is mitochondrial inheritance?

Mitochondria are little energy factories inside each cell that make energy for the body.

Apart from the DNA in the nucleus of each of our cells, there is also DNA present in the mitochondria. However, mtDNA is inherited only from the mother. That means if the mother’s mtDNA carries a mutation, she will pass it on to her children and, depending on the amount of mitochondria with the mutation, the children can be affected with mitochondrial disease.

Genetic testing

What is genetic testing?

It is possible to analyze an individual’s DNA to determine whether there are disease-causing mutations present. This analysis is called genetic testing. Depending on the type of mutation that is to be detected, the testing technique may vary. Sequencing is one of the most common techniques – it involves reading the DNA sequence letter by letter. This can reveal mutations like an insertion, deletion or a replacement of a total DNA segment.

Other techniques exist to test for larger insertions and deletions, and missing chromosomes. Another way to do genetic testing is by analyzing the products of these genes, i.e. proteins. For example, if an abnormal amount of a particular protein is produced, it could be because the gene associated with that protein is faulty.

How can genetic testing be useful to me?

• Genetic testing is the best and often only way to make an accurate and speedy diagnosis of rare genetic diseases.
• Genetic testing can reveal if you carry mutations that predisposes you to different genetic diseases.
• Genetic testing can predict the likelihood of you passing on a mutation to your children.
• If you have a genetic disease or carry a disease-causing mutation, other family members can then be tested. If they are aware of the risk, they can plan their lives better and obtain the support they need.
• If you have a family history of genetic disease and are planning to have children, it could be useful to conduct genetic tests before your child is born (before or during pregnancy).

How are genetic tests used?

Genetic tests may be used to identify increased risks of health problems, to choose treatments, or to assess responses to treatments.

What can I learn?

There are many different types of genetic tests. Genetic tests can help to:

• Diagnose disease
• Identify gene changes that are responsible for an already diagnosed disease
• Determine the severity of a disease
• Guide doctors in deciding on the best medicine or treatment to use for certain individuals
• Identify gene changes that may increase the risk to develop a disease
• Identify gene changes that could be passed on to children
• Screen newborn babies for certain treatable conditions