Genetics - How genetic conditions are inherited

Each cell in the body contains 23 pairs of chromosomes. One chromosome from each pair is inherited from your mother and one is inherited from your father.

The chromosomes contain the genes you inherit from your parents. There may be different forms of the same gene – called alleles.

For example, for the gene that determines eye colour, you may inherit a brown allele from your mother and a blue allele from your father. In this instance, you will end up with brown eyes because brown is the dominant allele. The different forms of genes are caused by mutations (changes) in the DNA code.

The same is true for medical conditions. There may be a faulty version of a gene that results in a medical condition, and a normal version that may not cause health problems.

Whether your child ends up with a medical condition will depend on several factors, including:

• what genes they inherit
• whether the gene for that condition is dominant or recessive (see below)
• their environment, including any preventative treatment they may receive

Genetic mutations

Genetic mutations occur when DNA changes, altering the genetic instructions. This may result in a genetic disorder or a change in characteristics.

Mutations can be caused by exposure to specific chemicals or radiation. For example, cigarette smoke is full of chemicals that attack and damage DNA. This causes mutations in lung cell genes, including the ones that control growth. In time, this can lead to lung cancer.

Mutations can also occur when DNA fails to be copied accurately when a cell divides.

Mutations can have three different effects. They may:

• be neutral and have no effect
• improve a protein and be beneficial
• result in a protein that does not work, which may cause disease

Passing on mutations

Some medical conditions are directly caused by a mutation in a single gene that may have been passed onto a child by his or her parents. These are known as monogenic conditions.

Depending on the specific condition concerned, monogenic conditions can be inherited in three main ways. These are outlined below.

Autosomal recessive inheritance

For conditions that are inherited in an autosomal recessive pattern to be passed on to a child, both parents must have a copy of the faulty gene (they are ‘carriers’ of the condition).

If the child only inherits one copy of the faulty gene, they will be a carrier of the condition but will not have the condition themselves.

If a mother and a father both carry the faulty gene, there is a one in four (25%) chance of each child they have inheriting the genetic condition and a one in two chance (50%) of them being a carrier.

Examples of genetic conditions inherited in this way include:

• cystic fibrosis – a condition in which the lungs and digestive system become clogged with thick sticky mucus
• sickle cell anaemia – a condition where red blood cells, which carry oxygen around the body, develop abnormally
• thalassaemia – a group of conditions where the part of the blood known as haemoglobin is abnormal, which means affected red blood cells are unable to function normally
• Tay-Sachs disease – a condition that causes progressive damage to the nervous system 

Autosomal dominant inheritance

For conditions that are inherited in an autosomal dominant pattern to be passed on to a child, only one parent needs to carry the mutation.

If one parent has the mutation, there is a one in two (50%) chance it will be passed on to each child the couple has.

Examples of genetic conditions inherited in this way include:

• type 1 neurofibromatosis – a condition that causes tumours to grow along the nerves
• tuberous sclerosis – a condition that causes mainly benign (non-cancerous) tumours to develop in different parts of the body
• Huntingdon's disease – a condition in which certain brain cells become increasingly damaged over time
• autosomal dominant polycystic kidney disease (ADPKD) – a condition that causes small, fluid-filled sacs called cysts to develop in the kidneys

X-linked inheritance

Some conditions are caused by a mutation on the X chromosome (one of the sex chromosomes). These are usually inherited in a recessive pattern – albeit in a slightly different way to the autosomal recessive pattern described above.

X-linked recessive conditions often don't affect females to a significant degree because females have two X chromosomes, one of which will almost certainly be normal and can usually compensate for the mutated chromosome. However, females who inherit the mutation will become carriers.

If a male inherits the mutation from his mother (males cannot inherit X-linked mutations from their fathers because they will receive a Y chromosome from them), he will not have a normal copy of the gene and will develop the condition.

When a mother is a carrier of an X-linked mutation, each daughter they have has a one in two (50%) chance of becoming a carrier and each son they have has a one in two (50%) chance of inheriting the condition.

When a father has an X-linked condition, his sons will not be affected because he will pass on a Y chromosome to them. However, any daughters he has will become carriers of the mutation.

Examples of genetic conditions inherited in this way include:

• Duchenne muscular dystrophy – a condition that causes the muscles to gradually weaken, resulting in an increasing level of disability
• haemophilia – a condition that affects the blood's ability to clot
• fragile X syndrome – a condition that usually causes certain facial and bodily characteristics, such as a long face, large ears and flexible joints

New mutations

Although genetic conditions are often inherited, this is not always the case. Some genetic mutations can occur for the first time when a sperm or egg is made, when a sperm fertilises an egg, or when cells are dividing after fertilisation. This is known as a 'de novo' or 'sporadic' mutation.

Someone with a new mutation will not have a family history of a condition, but they may be at risk of passing the mutation on to their children. They may also have, or be at risk of developing, a form of the condition themselves.

Examples of conditions that are often caused by a de novo mutation include some types of muscular dystrophy, haemophilia and type 1 neurofibromatosis.

Chromosomal conditions

Some conditions are not caused by a mutation on a specific gene, but by an abnormality in a person's chromosomes – such as having too many or too few chromosomes, rather than the normal 23 pairs.

Examples of conditions caused by chromosomal abnormalities include:

• Down's syndrome – a condition caused by having an extra copy of chromosome 21
• Edwards' syndrome – a condition caused by having an extra copy of one chromosome 18
• Turner syndrome – a condition that only affects females, caused by a missing or abnormal X chromosome
• Klinefelter's syndrome – a condition that only affects males, caused by extra X chromosome

While these are genetic conditions, they are generally not inherited. Instead, they usually occur randomly as a result of a problem before, during, or soon after the fertilisation of an egg by a sperm.

Multi-factorial conditions

Very few health conditions are only caused by genes – most are caused by the combination of genes and environmental factors. Environmental factors include lifestyle factors, such as diet and exercise.

Around a dozen or so genes determine most human characteristics, such as height and the likelihood of developing common conditions.

Genes can have many variants, and studies of the whole genome (the whole set of genes) in large numbers of individuals are showing that these variants may increase or decrease a person’s chance of having certain conditions. Each variant may only increase or decrease the chance of a condition very slightly, but this can add up across several genes.

In most people, the gene variants balance out to give an average risk for most conditions but, in some cases, the risk is significantly above or below the average. It is thought that it may be possible to reduce the risk by changing environmental and lifestyle factors.

For example, coronary heart disease (when the heart's blood supply is blocked or interrupted) can run in families, but a poor diet, smoking and a lack of exercise can also increase your risk of developing the condition.

Research suggests that in the future it will be possible for individuals to find out what conditions they are most likely to develop. It may then be possible for you to significantly reduce the chances of developing these conditions by making appropriate lifestyle and environmental changes.