Penetrance and expressivity

Classically, the genetic basis of the dependence of one gene on another is deduced from clear genetic ratios. However, only a small proportion of genes in the genome lend themselves to such analysis. One important property is that the mutation not exhibit decreased viability or fertility relative to wild type so that the frequency of recovery of mutant and wild-type classes are not skewed.

Another property is that the difference in the norm of reaction between mutant and wild type must be so dramatic that there is no overlap of the reaction curves for mutant and wild type, and hence we can reliably use the phenotype to distinguish mutant and wild-type genotypes with 100% certainty. In such cases, we say that this mutation is 100% penetrant. However, many mutations show incomplete penetrance. Thus penetrance is defined as the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype. For example, an organism may have a particular genotype but may not express the corresponding phenotype, because of modifiers, epistatic genes, or suppressors in the rest of the genome or because of a modifying effect of the environment. Alternatively, absence of a gene function may intrinsically have very subtle effects that are difficult to measure in a laboratory situation.

Another measure for describing the range of phenotypic expression is called expressivity. Expressivity measures the extent to which a given genotype is expressed at the phenotypic level. Different degrees of expression in different individuals may be due to variation in the allelic constitution of the rest of the genome or to environmental factors. Figure 4-23 illustrates the distinction between penetrance and expressivity. Like penetrance, expressivity is integral to the concept of the norm of reaction.

Figure 4-23. The effects of penetrance and expressivity through a hypothetical character “pigment intensity.

Figure 4-23

The effects of penetrance and expressivity through a hypothetical character “pigment intensity.” In each row, all individuals have the same allele—say, P—giving them the same “potential to produce pigment.” (more…)

Any kind of genetic analysis, such as human pedigree analysis and predictions in genetic counseling, can be made substantially more difficult because of the phenomena of incomplete penetrance and variable expressivity. For example, if a disease-causing allele is not fully penetrant (as is often the case), it is difficult to give a clean genetic bill of health to any individual in a disease pedigree (for example, individual R in Figure 4-24). On the other hand, pedigree analysis can sometimes identify individuals who do not express but almost certainly do have a disease genotype (for example, individual Q in Figure 4-24). Similarly, variable expressivity can confound diagnosis. A specific example of variable expressivity is found in Figure 4-25.

MESSAGE

The terms penetrance and expressivity quantify the modification of gene expression by varying environment and genetic background; they measure respectively the percentage of cases in which the gene is expressed and the level of expression.

Figure 4-24. Lack of penetrance illustrated by a pedigree for a dominant allele.

Figure 4-24

Lack of penetrance illustrated by a pedigree for a dominant allele. Individual Q must have the allele (because it was passed on to her progeny), but it was not expressed in her phenotype. An individual such as R cannot be sure that her genotype lacks (more…)

Figure 4-25. Variable expressivity shown by 10 grades of piebald spotting in beagles.

Figure 4-25

Variable expressivity shown by 10 grades of piebald spotting in beagles. Each of these dogs has SP, the allele responsible for piebald spots in dogs. (After Clarence C. Little, The Inheritance of Coat Color in Dogs. Cornell University Press, 1957; and (more…)

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Copyright © 2000, W. H. Freeman and Company.
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