Penetrance/Expressivity - Genetics

1. What is incomplete penetrance?

Incomplete penetrance occurs when not all individuals carrying a disease-causing genotype express the associated phenotype. For example, a person with a mutation in a dominant gene may not show the disease symptoms.

2. In an autosomal dominant disorder, disease allele A, if 8/10 of the Aa individuals show the disorder, what is the % penetrance? What is that in decimal form?

  • Penetrance = (Number of affected individuals / Total individuals with the genotype) × 100
    = (8/10) × 100 = 80%

  • Decimal form = 0.8

3. In an autosomal recessive disorder, disease genotype bb, if 8/10 of the bb individuals show the disorder, what is the % penetrance? What is that in decimal form?

  • Penetrance = (8/10) × 100 = 80%

  • Decimal form = 0.8

4. For X-linked disorder:

a. Do we need to worry about penetrance in males? Why?
No, for X-linked disorders in males, penetrance is generally straightforward because males have only one X chromosome. If the gene is present, the disorder is expressed.

b. Do we need to worry about penetrance in females? Why?
Yes, because females have two X chromosomes, one of which may carry the gene. Factors like X-inactivation and incomplete penetrance can influence whether the disorder manifests.

5. In an X-linked dominant disorder, disease allele XD, if 8/10 of the XD, Xd females show the disorder, what is the % penetrance? What is that in decimal form?

  • Penetrance = (8/10) × 100 = 80%

  • Decimal form = 0.8

6. In an X-linked recessive disorder disease allele Xd, with 60% penetrance:

a. How many XDXd females show the disorder? Why?
XDXd females are carriers and generally do not show symptoms for an X-linked recessive disorder. If they do, it is due to skewed X-inactivation.
With 60% penetrance, 60% of carriers show symptoms.

b. How many XdXd females show the disorder? What is that in decimal form?
All XdXd females have the disorder, but with 60% penetrance, only 60% of homozygous females express the condition.
In decimal form: 0.6

7. How does incomplete penetrance complicate genetic counseling and pedigree analysis?

Incomplete penetrance makes it difficult to predict whether an individual with a disease genotype will show symptoms. It can lead to underestimation of carrier status or confusion in identifying the inheritance pattern.

8. Ptosis (droopy eyes) is a dominant human trait. Among 40 heterozygotes, 13 have ptosis. What is the penetrance for this trait?

  • Penetrance = (13/40) × 100 = 32.5%

9. Two out of every four individuals who are homozygous for a recessive allele (r, r) develop the disease. What is the penetrance?

  • Penetrance = (2/4) × 100 = 50%

10. Assume that long ear lobes in humans are an autosomal dominant trait with 30% penetrance. A heterozygous person (Ee) mates with a homozygous normal (ee). What is the probability their 1st child will have long ear lobes?

  • Probability of passing the E allele = 50%

  • Probability of expressing the trait = 30%

  • Combined probability = 0.5 × 0.3 = 15%

11. A dominant trait in fish has 100% penetrance at 22°C and 42% at 26°C. If two heterozygous fish mate:

At 22°C:

  • Genotypic ratio for dominant phenotype = 3:1 (75% dominant phenotype)

  • Since penetrance is 100%, 75% of offspring will show the trait.

At 26°C:

  • Genotypic ratio for dominant phenotype = 75%

  • Adjusted by penetrance: 0.75 × 0.42 = 31.5% will show the trait.

12. How to calculate probability with reduced penetrance:

To calculate the probability of a phenotype:

  1. Determine the probability of inheriting the relevant genotype.

  2. Multiply it by the penetrance percentage.

For example:

  • If the probability of inheriting a genotype is 50% and penetrance is 60%, the overall probability of the phenotype is:
    0.5 × 0.6 = 0.3 (30%).