5.14 - Inherited Disorders

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.

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.