Virtual Medical Centre

Genetic Testing for Hereditary Diseases

• Introduction to genetics
• Types of genetic testing
• Methods and techniques used in genetic testing

Introduction to genetics

Almost every cell in our body contains a cell-nucleus that holds the 23 pairs of chromosomes that make up our genetic material. Each chromosome has within it the DNA (deoxyribonucleic acid) that makes up our hundreds of thousands of genes. Many of these genes make proteins that have a number of roles in the human body. Some proteins are structural and make up our tissues like bones and muscles. Proteins called enzymes are involved in chemical reactions like breaking down the food we eat. While others are like little messengers that send signals around our body, these proteins are known as hormones.

All humans share the same set of genes but the precise DNA sequence of these genes differs slightly between individuals (by about 0.1-0.2%). While these differences account for things like differing hair, eye and skin colour, they can also be the cause of genetic disease or disease susceptibility. A disease causing change in the DNA of a gene is called a mutation.

Types of genetic testing

Diagnostic tests

This is used to confirm a diagnosis when a doctor sees a patient with symptoms suggesting a particular genetic disease. For example, a person with a movement disorder may be tested for Huntington’s disease. The genetic information the doctor gets is useful in the treatment, management and genetic counselling of the patient.

Genetic screening tests

Some genetic tests are used even when symptoms of a disease are not seen, but the genetic information may help in predicting if the person is at risk of developing, or are susceptible to a particular disease.

1. Prenatal testing to screen for genetic diseases is offered to many women during pregnancy, a good example of this is the screening for Down syndrome in women over 35. Screening for Down syndrome is usually carried out by amniocentesis or chorionic villus sampling at 14 – 20 weeks of gestation.
2. Newborn screening is carried out routinely in most hospitals around the world, screening newborns for a number of disorders including phenylketonuria, cystic fibrosis (CF).. A blood sample is taken from the newborn, this blood sample is then sent to a laboratory for testing.
3. Carrier screening is used in people or populations to determine whether they carry a mutation (called a carrier) that may not affect the individual’s health but may affect the health of their future children. These mutations are usually recessive where both copies of the disease gene must be mutated in order for it to cause disease. In the case of an autosomal recessive disease, the child of a carrier will only have the disease if their partner is also a carrier. Carrier screening is offered to parents-to-be so that they can test if they are carriers for diseases such as cystic fibrosis (CF).

Methods and techniques used in genetic testing

Before a genetic test is carried out a doctor will do a clinical examination and get a detailed family history. This will help the doctor in working out which gene may be responsible for the disease in question. The patient will be referred to a genetic counsellor who can inform them about everything that is involved with genetic testing. The genetic counsellor can tell you what it means to have a particular genetic change and how this can affect you or your family.

Almost all genetic tests require a DNA sample from the patient, this is usually obtained by either a blood sample or mouthwash (buccal swab). This is then taken to a genetic testing lab for analysis.

A number of techniques are used in the process of genetic testing, these include:

Polymerase chain reaction (PCR) and DNA sequencing

The polymerase chain reaction (PCR) is a method of amplifying (copying) a small amount of DNA to a larger amount so that it can be analysedclosely. The genetic code of the DNA can be determined by a method called ‘DNA sequencing’. This then allows scientists to determine whether or not there is a change or mutation present in a gene of interest.

Indirect gene tracking (linkage analysis)

If the gene associated with a hereditary disease in a family is not known then linkage analysis can help in identifying the responsible gene. The technique is based on the fact that special DNA sequences that flank particular genes will travel with the gene when passed from parent to child. These DNA sequences are called ‘polymorphic markers’ or ‘polymorphic repeat sequences’. The closer that one of these markers is to gene the more likely it is that it is travelling with the gene. If a particular polymorphic marker is found only in members of a family with a particular disease then it is likely that a gene located near the marker is associated with the disease.