6.11 - 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:

Polydactyly, a dominant inherited disorder

• Polydactyly is a genetic disorder in which a baby is born with extra fingers or toes.
• It doesn't usually cause any other problems and is not life-threatening.

Caused by a dominant allele

• Polydactyly is caused by a dominant allele, usually written as an uppercase D.
• Because the allele is dominant, a person needs only one copy to have the disorder - so it can be inherited even when just one parent carries the faulty allele.
• That parent will also have the condition themselves, because a single dominant allele is enough to cause it.
• This is the opposite of a recessive disorder: there are no hidden carriers of a dominant disorder, because anyone carrying the allele shows the condition.

Example - Affected parent (Dd) × unaffected parent (dd)

One parent has a single dominant allele (Dd) and shows polydactyly; the other has two normal alleles (dd) and is unaffected.

• Each child has a 1 in 2 (50%) chance of inheriting the dominant allele and having polydactyly.
• Each child has a 1 in 2 (50%) chance of inheriting only normal alleles and being unaffected.
• Half the offspring are heterozygous and affected, half are homozygous recessive and unaffected - a 1:1 ratio.

Screening embryos before implantation

• Embryo screening detects some genetic disorders in an embryo before a baby is born.
• During in vitro fertilisation (IVF), egg cells are fertilised by sperm in a laboratory rather than inside the body, and the embryos are later transferred into the woman's uterus.
• Before an embryo is transferred, a single cell can be removed and its genes analysed. Many disorders, including cystic fibrosis, can be detected this way.
• DNA can also be taken from an embryo already developing in the uterus and tested for disorders.

What happens next depends on the result

• For an IVF embryo: one found to carry alleles linked to a disorder would be discarded, and a different, unaffected embryo used instead.
• For an embryo already in the uterus: a positive result could lead to a decision to terminate the pregnancy.
• Because of these decisions, embryo screening is controversial, raising ethical, social, and economic concerns on both sides.

Arguments for and against

At present there are laws that limit how far screening can go - for example, parents cannot select the sex of their baby unless there is a medical reason.