Inherited disorders

Cystic fibrosis

Cystic fibrosis is an inherited disorder of cell membranes that mainly affects the lungs and digestive system. They can become clogged with lots of thick, sticky mucus as too much is produced. Over many years, the lungs become increasingly damaged and may eventually stop working properly. A number of treatments are available to help reduce the problems caused by the condition, but unfortunately average life expectancy is reduced for people who have it.

It is caused by a faulty recessive allele on chromosome 7. To be born with cystic fibrosis, a child has to inherit two copies of this faulty gene - one from each of their parents. Their parents will not usually have the condition themselves, because they will only carry one faulty gene and one that works normally.

In the diagram below cystic fibrosis involves:

• the recessive allele (lower case), which can be shown as f
• the dominant allele (capital letter), which can be shown as F

An individual who is homozygous (ff) with the recessive allele will develop cystic fibrosis. Someone who is heterozygous (Ff) will be a carrier of the recessive allele, but will not develop cystic fibrosis and have no symptoms. Someone who is homozygous with the dominant allele (FF) will not develop cystic fibrosis, as you need two faulty alleles (ff) for the condition. In this combination, no faulty alleles are present.

Example 1

In example 1, both parents are heterozygous, Ff. The chance of them producing a child with cystic fibrosis is 1 in 4, or 25%. The parents are carriers of the disorder, and it is possible for them to produce a child with cystic fibrosis, without having it themselves. Carriers have no symptoms and are usually unaware they are carrying the recessive allele.

Example 2

In example 2, only one parent (the father) has a copy of the recessive allele (Ff). There is no chance of them producing a child with cystic fibrosis. However, half the possible offspring will be homozygous, FF, and be unaffected, and half will be heterozygous, Ff and carry the recessive allele. The ratio of FF to Ff is 1:1 or 50%.

This genetic diagram shows how cystic fibrosis is inherited.

Polydactyly

Polydactyly is an inherited condition in which a person has extra fingers or toes. It is caused by a dominant allele of a gene. This means it can be passed on by just one allele from one parent if they have the disorder.

Someone who is homozygous (PP) or heterozygous (Pp) for the dominant allele will develop polydactyly.

Offspring need to carry just one dominant allele from their parents to inherit the polydactyly condition.

The probability of the offspring having polydactyly is 50% (2 of the 4) and 50% not having it (normal). This can be expressed as a ratio, 2:2 which can be simplified to 1:1.

Genetic tests

Genetic testing involves analysis of a person's DNA to see if they carry alleles that cause genetic disorders. It can be done at any stage in a person's life.

• Antenatal testing is used to analyse an individual's DNA or chromosomes before they are born. This testing is offered to couples who may have an increased risk of producing a baby with an inherited disorder, but it can't detect all the risks of inherited disorders.
• Neonatal testing known as the new born blood spot test involves analysing a sample of blood that is taken from pricking a baby's heel. It detects genetic disorders in order to treat them early.
• Pre-implantation genetic diagnosis (PGD) is used on embryos before implantation. Fertility drugs stimulate the release of several eggs. The eggs are collected and fertilised in a Petri dish. This is known as in vitro fertilisation (IVF). Once the embryos have reached the eight-cell stage, one cell is removed.
• The cells are tested for the disorder-causing alleles. Embryos that don't contain the disorder allele are implanted into the uterus.