11.12 - Inherited Disorders & Screening

Cystic fibrosis, a recessive inherited disorder

• Cystic fibrosis is a genetic disorder of the cell membranes, caused by the mutation of a single gene.
• The faulty protein this gene makes can no longer properly control the movement of salt and water into and out of cells.
• As a result, the body produces a lot of thick, sticky mucus that builds up in:
  • The air passages of the lungs (the bronchioles)
  • The pancreas
• This leads to frequent, serious lung infections and to problems with digesting food.

A recessive allele

• The disorder is caused by a recessive allele, usually written as a lowercase f.
• Because the allele is recessive, a person only has cystic fibrosis if they inherit two copies of it - so an affected person is homozygous recessive (ff).
• A person with just one copy (Ff) does not have the disorder, because the normal dominant allele still works. They are called a carrier and can pass the faulty allele on.
• The recessive allele is fairly common - about 1 person in 25 carries it, so many carriers have no idea they could pass it on.

Inheriting cystic fibrosis

• For a child to be born with cystic fibrosis, both parents must each pass on a recessive allele - so both must be carriers or have the disorder themselves.
• Crossing two carriers (Ff × Ff) gives four equally likely combinations: FF, Ff, Ff and ff.

For any one child, the chances of each outcome are:

Huntington's disease and Down's syndrome

Some inherited disorders are caused by a dominant allele rather than a recessive one, and Huntington's disease is one of these. Down's syndrome arises differently again, from a whole extra chromosome.

Huntington's disease - A dominant allele

• Caused by a faulty dominant allele, so only one copy is needed to develop the condition.
• An affected parent can pass it on directly.
• It causes progressive deterioration of the brain, which usually doesn't appear until middle age.
• It is fatal, with currently no cure.
• Because symptoms appear late in life, a person may already have had children before they know they carry the allele.

Down's syndrome - An extra chromosome

• Not caused by a faulty allele at all, but by a whole extra chromosome.
• People normally have 46 chromosomes in their body cells, and each gamete (sperm or egg) normally carries 23.
• Occasionally a gamete forms with 24 chromosomes instead of 23. If it fertilises a normal gamete, the child has 47 chromosomes rather than 46 - this causes Down's syndrome.
• Features include a distinctive facial appearance, reduced muscle tone, and reduced cognitive development.

How Down's syndrome differs from inherited disorders

• It comes from a mistake during gamete formation, not from passing on a particular allele, so it isn't inherited in the way cystic fibrosis and Huntington's disease are.
• It can be identified using a karyotype - a display of all a person's chromosomes - by counting them to find the extra chromosome.

Prenatal screening - Amniocentesis and the blood test

• Genetic screening checks whether a foetus in the womb has a genetic condition - such as Down's syndrome or cystic fibrosis - before the baby is born.
• Two methods are used: a blood test and amniocentesis.

The blood test

• Offered to a pregnant woman first, after about 10 to 14 weeks of pregnancy.
• The result estimates whether the chance of the baby having a condition such as Down's syndrome is higher than normal.
• It carries no risk to the mother or the foetus, but it's less accurate - it doesn't give a definite answer, only flags who is at higher risk.
• Women shown to be at higher risk are then offered the more accurate but riskier amniocentesis.

Amniocentesis

• The fluid around the foetus, called amniotic fluid, is held in the amnion and contains some of the foetus's own cells.
• A sample of this fluid is taken, the cells are grown in the laboratory, and the number of chromosomes in each cell is counted - for example to detect the extra chromosome of Down's syndrome.
• It gives a more accurate result than the blood test, but carries a risk of about 1 in 100 (1%) of causing a miscarriage.

The ethics of prenatal screening

When screening diagnoses a genetic condition, parents face a difficult decision about whether to continue the pregnancy, and people disagree strongly about what is right.

Screening raises wider questions too:

• Who should decide who is screened?
• What level of risk is acceptable?
• Should the cost of screening be weighed against the cost of treating people with a condition?
• Should genetic information be made available to wider society - for instance, insurance companies could use it to refuse cover or charge more?