From the Guidelines
Penetrance in genetics refers to the proportion of individuals with a specific genotype who exhibit the expected phenotype, with complete penetrance meaning everyone with the disease-causing genotype shows symptoms, and incomplete penetrance occurring when some individuals with the genotype remain asymptomatic. This concept is crucial for genetic counseling, as it helps predict the likelihood that someone carrying a disease-causing mutation will actually develop the condition, and is influenced by factors such as environmental factors, modifier genes, age, and sex 1.
Key Considerations
- Penetrance is one among several criteria considered in the selection of secondary findings gene-disease pairs, alongside factors such as phenotype severity and burden of potential treatments 2.
- Penetrance data derived from populations are the most directly applicable to secondary findings list consideration, and ideally should be derived from population-scale cohorts with acknowledged recruitment biases, genomic ascertainment, and clear variant classification 3.
- Understanding penetrance is essential for risk assessment in hereditary conditions and explains why some family members with the same genetic mutation may have different clinical outcomes.
Importance of Penetrance
Penetrance differs from expressivity, which describes the varying severity of symptoms among individuals who do express the phenotype. For example, BRCA1 mutations have approximately 80% penetrance for breast cancer, meaning about 80% of mutation carriers will develop the disease. The consideration of penetrance data is critical in genetic counseling, as it helps individuals understand their risk of developing a condition and make informed decisions about their health 1.
Factors Influencing Penetrance
- Environmental factors
- Modifier genes
- Age
- Sex These factors can influence the likelihood of an individual with a specific genotype exhibiting the expected phenotype, and should be considered when interpreting penetrance data 1, 2, 3.
From the Research
Definition of Penetration in Genetics
- Penetration, also known as penetrance, refers to the percentage of individuals with a specific genotype who express the associated phenotype 4.
- In other words, penetrance is a measure of the proportion of individuals with a particular genetic variant who actually develop the corresponding trait or disease.
Factors Influencing Penetrance
- Penetrance can be influenced by genetic and environmental factors, leading to incomplete penetrance and variable expressivity 4.
- Incomplete penetrance occurs when some individuals with a specific genotype do not express the associated phenotype, while variable expressivity refers to the degree to which a genotype is expressed as a phenotype within an individual.
Examples of Penetrance
- A study on genetically epilepsy-prone rats found that the GEPR-3 and GEPR-9 strains showed incomplete penetrance and variable expressivity of the underlying genetic predisposition to epilepsy 4.
- The study found that the GEPR-9 strain had a greater percentage of animals that exhibited no susceptibility to sound-induced seizures, while the GEPR-3 animals showed smaller differences in penetrance and expressivity.
Relevance to Human Genetics
- While the provided studies primarily focus on hypertrophic cardiomyopathy and genetic testing, the concept of penetrance is relevant to various genetic disorders, including those caused by DNA mutations 5.
- Understanding penetrance is essential for predicting the likelihood of an individual developing a particular disease or trait based on their genetic profile.