Penetrance

SIGNIFICANCE: Penetrance is a measure of how frequently a specific genotype results in the same, predictable phenotype. Such variable expression of the same genotype is the result of different genetic backgrounds and the effects of variations in the environment. Geneticists desire 100 percent penetrance for desirable genes that offer disease resistance but reduced penetrance and low expressivity for others that may contribute to human diseases.

Gene Expression and Environment

Gene expression results in a chemical product (protein) with a specific function. The genotype (genetic makeup, or gene) and environmental conditions determine the phenotype of an individual.

Penetrance and Expressivity

Gene expression is dependent upon environmental factors and may be modified, enhanced, silenced, and/or timed by the regulatory mechanisms of the cell in response to internal and external forces. A range of phenotypes can result from a genotype in response to different environments; the phenomenon is called “norms of reaction” or “phenotypic plasticity.” Norms of reaction represent the expression of phenotypic variability in individuals of a single genotype.

The question of which is more important in the formation of an organism, nature (genotype) or nurture (environment), has been debated for centuries. The answer is that it depends. The genotype defines phenotypic potential. The environment works on the plasticity of expression to produce different phenotypes from similar genotypes.

Penetrance is the proportion of individuals with a specific genotype who display a defined phenotype. Some individuals may not express a gene if modifiers, epistatic genes, or suppressors are also present in the genome. Penetrance is the likelihood, or probability, that a condition or disease phenotype will, in fact, appear when a given genotype is present. If every person carrying a gene for a dominantly inherited disorder has the mutant phenotype, then the gene is said to have 100 percent penetrance. If only 30 percent of those carrying the mutant allele exhibit the mutant phenotype, the penetrance is 30 percent. Sometimes an individual with a certain genotype fails to express the expected phenotype, and then the allele is said to be nonpenetrant in the individual. If the phenotype is expressed to any degree, the genotype is penetrant.

Given a particular phenotypic trait and a genotype, penetrance can be expressed as the probability of the phenotype given the genotype. For example, penetrance can be the probability of round seeds, a phenotype, given the genotype G; it can also be the probability of wrinkled seeds, another phenotype, given the genotype G. One could label the specific phenotype of interest as Pii (Pi might refer to either the round or wrinkled seeds) and the specific genotype among many possibilities as Gj. The penetrance would then be the probability of Pii given Gj. These penetrances can all be expressed using the mathematical notation of conditional probabilities as follows:

Case 1: Pr(round|G)Case 2: Pr(wrinkled|G)Case 3: Pr(Pii|Gj)

A 100 percent penetrance means that all individuals who possess a particular genotype express the phenotype (common in all homozygous lethal genes). Tay-Sachs disease shows complete, or 100 percent, penetrance, as all homozygotes for this allele develop the disease and die.

An allele, Fu, in mice causes fusion in the tail in heterozygotes, Fufu, and extremely fused and abnormal tails in the homozygotes, FuFu. From testcross matings of Fufu × fufu, 87 fused-tailed mice and 129 nonfused-tailed mice resulted. Genetic analyses of the 129 nonfused-tailed mice revealed that 22 were genotypically Fufu. The number of fused-tailed mice was 87 and the number of mice with the Fufu genotype but nonfused tails was 22. The total number of fused-tailed mice expected was (87 + 22) = 109. Therefore, penetrance was calculated at 87/109 = 0.798

Expressivity

Whereas penetrance describes the frequency with which a genotype is expressed as a specified phenotype, expressivity describes the range of variation in the phenotype when expression is observed. Expressivity is variation in allelic expression when the allele is penetrant. Not all traits are expressed 100 percent of the time even though the allele is present. Expressivity is the range of variation in a phenotype; it refers to the degree of expression of a given trait or combination of traits that is associated with a gene. Affected individuals may have severe or mild symptoms; they may have symptoms that show up in one organ or combination of organs in one individual but not in the same locations in other individuals.

Phenotype may be altered by heterogeneity of other genes that affect the expression of a particular locus in question, or by environmental influence. Variable expressivity is a common feature of a variety of cancers. The lower the penetrance, the fewer individuals will be affected. In humans, the dominant allele P produces polydactyly—extra toes and/or fingers. Matings between two normal appearing parents sometimes produce offspring with polydactyly. The parent with the Pp genotype exhibits reduced penetrance for the P allele.

Key terms

• expressivitythe degree to which a phenotype is expressed, or the extent of expression of a phenotype
• phenotypethe physical appearance or biochemical and physiological characteristics of an individual, which is determined by both heredity and environment

Bibliography

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