6.4 Penetrance and Expressivity

In the analysis of single-gene inheritance, there is a natural tendency to choose mutants that produce clear Mendelian ratios. In such cases, we can use the phenotype to distinguish mutant and wild-type genotypes with almost 100 percent certainty. In these cases, we say that the mutation is 100 percent penetrant into the phenotype. However, many mutations show incomplete penetrance: that is, not every individual with the genotype expresses the corresponding phenotype. Thus, penetrance is defined as the percentage of individuals with a given allele who exhibit the phenotype associated with that allele.

Figure 6-21: Inferring incomplete penetrance
Figure 6-21: In this human pedigree of a dominant allele that is not fully penetrant, person Q does not display the phenotype but passed the dominant allele to at least two progeny. Because the allele is not fully penetrant, the other progeny (for example, R) may or may not have inherited the dominant allele.

Why would an organism have a particular genotype and yet not express the corresponding phenotype? There are several possible reasons:

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  1. The influence of the environment. Individuals with the same genotype may show a range of phenotypes, depending on the environment. The range of phenotypes for mutant and wild-type individuals may overlap: the phenotype of a mutant individual raised in one set of circumstances may match the phenotype of a wild-type individual raised in a different set of circumstances. Should this matching happen, the mutant cannot be distinguished from the wild type.

  2. The influence of other interacting genes. Uncharacterized modifiers, epistatic genes, or suppressors in the rest of the genome may act to prevent the expression of the typical phenotype.

  3. The subtlety of the mutant phenotype. The subtle effects brought about by the absence of a gene function may be difficult to measure in a laboratory situation.

A typical encounter with incomplete penetrance is shown in Figure 6-21. In this human pedigree, we see a normally dominantly inherited phenotype disappearing in the second generation only to reappear in the next.

Figure 6-22: Penetrance and expressivity contrasted
Figure 6-22: Assume that all the individuals shown have the same pigment allele (P) and possess the same potential to produce pigment. Effects from the rest of the genome and the environment may suppress or modify pigment production in any one individual. The color indicates the level of expression.

Another measure for describing the range of phenotypic expression is called expressivity. Expressivity measures the degree to which a given allele is expressed at the phenotypic level; that is, expressivity measures the intensity of the phenotype. For example, “brown” animals (genotype b/b) from different stocks might show very different intensities of brown pigment from light to dark. As for penetrance, variable expressivity may be due to variation in the allelic constitution of the rest of the genome or to environmental factors. Figure 6-22 illustrates the distinction between penetrance and expressivity. An example of variable expressivity in dogs is found in Figure 6-23.

The phenomena of incomplete penetrance and variable expressivity can make any kind of genetic analysis substantially more difficult, including human pedigree analysis and predictions in genetic counseling. For example, it is often the case that a disease-causing allele is not fully penetrant. Thus, someone could have the allele but not show any signs of the disease. If that is the case, it is difficult to give a clean genetic bill of health to any person in a disease pedigree (for example, person R in Figure 6-21). On the other hand, pedigree analysis can sometimes identify persons who do not express but almost certainly do have a disease genotype (for example, individual Q in Figure 6-21). Similarly, variable expressivity can complicate counseling because persons with low expressivity might be misdiagnosed.

Figure 6-23: Variable expressivity
Figure 6-23: Ten grades of piebald spotting in beagles. Each of these dogs has the allele SP, the allele responsible for piebald spots in dogs. The variation is caused by variation at other loci.

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Even though penetrance and expressivity can be quantified, they nevertheless represent “fuzzy” situations because rarely is it possible to identify the specific factors causing variation without substantial extra research.

KEY CONCEPT

The terms penetrance and expressivity quantify the modification of a gene’s effect by varying environment and genetic background; they measure, respectively, the percentage of cases in which the phenotype is observed and its severity.