Genetic inheritance and testing

What does genetics mean? Our bodies are made up of thousands of different proteins that all together make each one of us unique. The nature of each protein is determined by a special code which is carried on molecules of DNA. Every cell carries the DNA coding for all proteins in the body, but only the parts of the code that are relevant to that cell are then translated into proteins. The part of the DNA that carries the code for the cell is called a gene. Genes are arranged end to end along a length of DNA called a chromosome. You inherit a copy of your genes from each of your parents. It may help to think of yourself as a book: The chromosomes are the chapters. There are 22 pairs of chromosomes and one pair of sex chromosomes, so 23 chapters. The genes are coding for proteins that dictate characteristics like hair and eye colour or your height. The coding is like the words in the chapters. The code in your DNA is like the letters in the words. The way these letters are arranged can influence your risk of developing conditions such as high blood pressure or heart disease. For example, the words BARE and BEAR have the same letters, but theyre arranged differently so they mean different things. In the same way, if the codes in the DNA are arranged differently, they may work in different ways. What is the link between genes and heart conditions? If one of your genes has a mistake in it a bit like a spelling mistake in a word it could lead to an abnormal protein being produced in that particular type of cell. The same mistake will be passed on to the next and following generations. We inherit one copy of each gene from each of our parents. If you have a correctly spelt gene from one of your parents, it might compensate for an incorrectly spelt gene in the copy from the other parent. So, a person may not be aware that they are carrying a gene that could lead to a particular disease or condition. This is how abnormal genes can be passed on silently (without anyone knowing) from one generation to another. They are called recessive genes. If both your parents have a gene with the same mistake in it, this will result in you having an abnormal protein, which may cause a particular disease or condition. Sometimes, a gene with a mistake in it can produce an abnormal protein, even if the

Genetic inheritance and testing

other copy of the gene is normal. The abnormal gene is known as a dominant gene. Some rare heart conditions are caused by serious mistakes known as mutations in a single gene. For example, hypertrophic cardiomyopathy is caused by a mutation in a dominant gene that produces an abnormal protein in the heart cells. This results in thickening of the heart wall and makes the person more prone to sudden death. However, most heart conditions are caused by the interaction of many subtle spelling mistakes. So its like having the same word with the same meaning, but spelt slightly differently for example, COLOUR and COLOR. What is a genetic test? A genetic test is a test that is carried out on a sample of your DNA. The DNA is taken from a sample of cells or from a blood sample. The test will look at the sample to investigate if a specific gene is spelt correctly. If a mistake is found, a test can also be carried out on other family members to see if they have the same gene mutation. Genetic counsellors (specialists in genetic medicine) will explain, to people who have a genetically determined disease, how likely it is that they will pass the abnormal gene on to their children. Brothers and sisters of the affected person can also be affected and will also be tested. In most single-gene defects (that is, defects that are caused by a single gene), the condition is likely to develop if a person has a mutation. In polygenic disorders (that is, conditions that are caused by a combination of several different defective genes), the condition or disease is more likely to be caused by the interaction between lifestyle behaviours such as smoking, diet or lack of physical activity and the interaction of mutations in several different genes. There are good, accurate genetic tests available for certain conditions such as hypertrophic cardiomyopathy, Marfans syndrome and familial hyperlipidaemia (see below). Mutations of specific genes have been identified. This allows doctors to diagnose if you have a condition that is caused by one of those genes. So, if you have genetic testing and you are found to have the mutation, you have the condition although it may not be immediately obvious. How severe the condition is may vary from one person to another, and you can pass on the condition. If you dont have the mutation, you dont have the disease and you cannot pass it on.

Genetic inheritance and testing

Genetic testing and screening should only be undertaken following advice from a genetic specialist and counsellor who can make sure that the right test is done and that the results are interpreted correctly. Buying genetic tests without the appropriate support and guidance could give misleading and inaccurate information. Conditions caused by single-gene defects Hypertrophic cardiomyopathy affects about 1 in every 500 people in the UK. In people with this condition, the heart muscle thickens, and this may lead to serious abnormal heart rhythms. This condition has a dominant inheritance pattern. This means that if a child has one parent with cardiomyopathy but the other parent does not have the condition, the child will have a 1 in 2 chance of inheriting the condition. Affected families are sometimes genetically screened using a blood test which may determine if someone is carrying the affected gene. The testing can help to reassure people who are worried about their family history. Marfans syndrome is an inherited disease which affects the connective tissue of different parts of the body including the heart, blood vessels, skeleton and eyes. It has a dominant inheritance pattern, which means that the children of a person with this syndrome will have a 1 in 2 chance of inheriting it. Families with Marfans syndrome may need genetic counselling and screening as they have a greater risk of developing an aneurysm (a weakening or swelling of an artery wall). Familial hyperlipidaemia occurs in about 1 in 500 adults in the UK. It is an inherited disorder which may lead to premature coronary heart disease. Familial hyperlipidaemia affects the way in which low density lipoproteins (LDL or harmful cholesterol) are removed from the blood. People with this condition have an abnormally high cholesterol level which will need to be treated with medication.

If you think you may have an inherited heart condition and would like to speak to someone from our genetic information service please call 0300 456 8383 Mon Fri 0900 1800. Calls charged at a local rate.

Genetic inheritance and testing

What about coronary heart disease? Coronary heart disease is caused by variations in lots of different genes. So it is a polygenic disease (see above). Coronary heart disease is caused by the build-up of atheroma (fatty deposits) in the coronary arteries. Unlike the three conditions mentioned above, there is no specific genetic test for coronary heart disease because many different factors contribute to its development. These things are called risk factors. The risk factors for coronary heart disease are: smoking high blood pressure raised cholesterol being overweight physical inactivity diabetes family history of coronary heart disease. Many of the risk factors listed above may be due to your lifestyle for example, smoking or not taking enough physical activity. So, making lifestyle changes will reduce your risk of developing heart disease. However, some people are more susceptible to high blood pressure or to developing diabetes and so their risk of developing heart disease may have a genetic link. For example, high blood pressure and diabetes are thought to be due to minor spelling mistakes in multiple genes. On their own, they may not cause the condition, but when they occur in clusters, they increase the risk of the person getting the condition. This is why there are no reliable genetic tests for these conditions. So, while currently there is no specific genetic test for coronary heart disease, everyone should take steps to reduce their overall risk by examining their lifestyle and adjusting the factors that may increase their risk. What about the future? In the near future, genetic screening is likely to help many families where there is a family history of coronary heart disease or of structural heart defects. Blood tests capable of detecting genetic mutations are being developed. Those people who are genetically prone to heart disease, high blood pressure and diabetes could then be identified. The British Heart Foundation is helping to fund research into the rogue genes that may contribute to coronary heart disease. However, the results of this research will

Genetic inheritance and testing

not be available for several years. For more information
British Heart Foundation booklets Keep your heart healthy Put your heart into walking So you want to lose weight for good Useful organisations Cardiomyopathy Association Unit 10 Chiltern Court Asheridge Road Chesham Bucks HP5 2PX Phone: 0800 018 1024 Email: info@cardiomyopathy.org Website: www.cardiomyopathy.org Heart UK 7 North Road Maidenhead Berkshire SL6 1PE Helpline: 0845 450 5988 Email: ask@heartuk.org.uk Website: www.heartuk.org.uk For information on hyperlipidaemia. Marfan Association UK Rochester House 5 Aldershot Road Fleet Hampshire GU51 3NG Phone: 01252 810472 Answerphone 01252 617320 Email: marfan@tinyonline.co.uk Website: www.marfan-association.org.uk

March 2009.