Autosomal inheritance

Dominant

• Only one copy required to cause disease, disease seen in all generations
• A person affected by an autosomal dominant disorder has a 50% chance of passing the mutated gene to each child

Recessive

• 2 copies of faulty gene required to cause disease, often only 1 generation affected
• 1 in 4 risk of child being affected if parents are carriers

X linked inheritance

• Gene fault lies on X chromosome
• X-linked recessive inheritance - a female with one pathogenic allele and one normal allele does not show major clinical features of the disease, but a male with a single faulty allele will be fully affected
  • Carrier female may have an unaffected son (1/4), affected son (1/4), unaffected daughter (1/4), carrier daughter (1/4)
  • If an affected male has children, all his daughters will be carriers and all his sons will be unaffected (no male-male transmission)
• Female carrier may show mild features – X inactivation (around ½ of cells will have faulty gene)

Mitochondrial inheritance

• The mitochondria in the cell have their own genome (single loop)
• In many cases, a mutation in the mitochondrial genome is only present in a proportion of the mitochondria, and the proportion varies between cells within an individual
• Mitochondrial DNA is transmitted maternally, in the ovum

Pedigree trees

How mutations cause disease

• Haploinsufficiency: only one copy of working gene, reduced protein production
• Dominant negative: expression of abnormal protein interferes with normal protein