Patterns of Inheritance

There are several different types of inheritance patterns with different underlying mechanisms. These may involve:

  • single nuclear genes (autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant)
  • single mitochondrial genes
  • chromosomal rearrangements
  • imprinting
  • multifactorial inheritance

Autosomal Dominant

  • Vertical transmission, from one generation to the next
  • Female and males equally affected
  • Male to male transmission possible
  • Heterozygotes are phenotypically affected
  • Each child has a 50% chance of inheriting the gene mutation
  • Variable expression (severity of disease) due to modifiers (genetic and environmental)
  • Anticipation is a worsening of disease severity in successive gen-erations

Examples of this are:

  • dominant polycystic kidney disease
  • myotonic dystrophy
  • marfan syndrome
  • Huntington’s disease
  • neurofibromatosis type 1
  • familial adenomatous polyposis
  • familial breast cancer

Autosomal Recessive

  • Usually affected siblings in one generation only, unless consan-guineous family or high population carrier frequency
  • Female and males equally affected
  • Carriers usually unaffected, i.e. healthy carriers
  • Carriers may have a survival advantage, e.g. sickle cell trait and malaria protection
  • When both parents are carriers, each child has a 1 in 4 chance of developing phenotype, unaffected offspring have 2 in 3 carrier risk
  • All offspring of affected individuals will be obligate carriers

Examples of this are:

  • cystic fibrosis
  • thalassaemia
  • most inborn errors of metabolism
  • alpha1-antitrypsin deficiency

X-linked Recessive

  • Males more severely affected than females
  • Females may be affected if skewed X inactivation
  • No male to male transmission
  • For carrier female, each son and each daughter has 50% chance of inheriting the gene mutation
  • For affected males, all sons will be unaffected and all daughters will be carriers

Examples of this are:

  • duchenne muscular dystrophy
  • haemophilia
  • red-green colour blindness
  • fragile X syndrome
  • Alport syndrome

X-linked Dominant

  • Often lethal in males
  • Carriers females affected and more severe if skewed X inactivation
  • No male to male transmission
  • For carrier female, each son and each daughter has 50% chance of inheriting the gene mutation
  • For surviving affected male, all sons will be unaffected and all daughters will be affected

Examples of this are:

  • X-linked hypophophatasia
  • incontinentia pigementi
  • Rett syndrome

Polygenic disorders

Genetic disorders resulting from the combined action of alleles of more than one gene (e.g., heart disease, diabetes, and some cancers).

Although such disorders are inherited, they depend on the simultaneous presence of several alleles; thus the hereditary patterns are usually more complex than those of single-gene disorders. Compare single-gene disorders.


  • Development of disease depends on genetic and environmental factors
  • Risk greatest amongst close relatives and decreases with increasing distance of relationship
  • Risks to relatives greater if proband severely affected
  • If 2 or more affected relatives, increased risk to relatives

Examples of this are:

  • ischaemic heart disease
  • type 1 diabetes
  • schizophrenia

Mitochondrial Disease

Mitochondrial diseases can be highly problematic. Mitochondrial disorders can be coded for by the nuclear genome. The incidence of mitochondrial respiratory chain diseases is

Under the age 6    =    1 in 1000
Under age 16          =    1 in 21000
Adults                        =    1 in 8000

Mitochondrial DNA (mtDNA) is a circular double stranded molecule encoding 37 genes, 13 of which encode components of the oxidative phosphorylation (OXPHOS) system. Typical cells can conatain up to 1000 mitohondria each with one or several copies of the mtDNA genome.

The organs most affected by mitochondrial diseases are those affecting high energy tissue such as the CNS, muscle, pancreas , liver and kidneys.

Mitochondrial inheritance

  • The disorder can affect males and females equally
  • MtDNA is almost exclusively maternally inherited
  • Any paternal mitochondria entering at fertilization from sperm is later eliminated
  • Male to male transmission is possible but exceedingly rare
  • Variable penetrance (frequency of developing the phenotype) and variable expression (severity of disease) are due to genetic and environmental modifiers.