Penetrance/Expressivity - Genetics

Incomplete penetrance

Occurs when not all individuals carrying a disease-causing genotype express the associated phenotype.

Penetrance in autosomal dominant disorder

Percentage of individuals with a genotype expressing the phenotype; for example, if 8 out of 10 individuals show the disorder, penetrance is 80%.

Penetrance in autosomal recessive disorder

Percentage of individuals with the recessive genotype expressing the disorder; for example, if 8 out of 10 individuals show the disorder, penetrance is 80%.

Penetrance in males for X-linked disorders

Generally straightforward because males have only one X chromosome; if the gene is present, the disorder is expressed.

Penetrance in females for X-linked disorders

More complex due to two X chromosomes; factors such as X-inactivation and incomplete penetrance affect manifestation.

X-linked dominant disorder penetrance calculation

If 8 out of 10 females (XD, Xd) show the disorder, the penetrance is 80%.

X-linked recessive disorder and carriers

XDXd females are typically carriers and may not show symptoms unless there’s skewed X-inactivation; with 60% penetrance, 60% might show symptoms.

Homozygous females and X-linked recessive disorder

All XdXd females have the disorder, but only 60% express it due to 60% penetrance.

Genetic counseling and incomplete penetrance

Makes it challenging to predict symptom manifestation in individuals with disease genotypes, complicating carrier status and inheritance patterns.

Penetrance for ptosis trait

If among 40 heterozygotes, 13 have ptosis, the penetrance is 32.5%.

Penetrance = (13/40) × 100 = 32.5%

Penetrance in homozygous recessive individuals

If 2 out of 4 homozygous recessive individuals develop the disease, the penetrance is 50%.

Probability of long ear lobes (Ee x ee)

For a heterozygous parent (Ee) and a homozygous normal (ee), the probability their first child will have long ear lobes (30% penetrance) is 15%.

• Probability of passing the E allele = 50%

• Probability of expressing the trait = 30%

• Combined probability = 0.5 × 0.3 = 15%

Calculating probability with reduced penetrance

Multiply the probability of inheriting the relevant genotype by the penetrance percentage to find the overall phenotype probability.