Book Viewer

Short Contents | Full Contents | Other books @ NCBI

Modern Genetic Analysis Chapter 6. Gene Interaction
Penetrance and Expressivity

In the previous examples, the genetic basis of the dependence of one gene on another has been deduced from clear genetic ratios. However, only a relatively small proportion of genes in the genome exhibit properties that make them favorable for 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 is not skewed.

Another property is that the difference in the norm of reaction (see Chapter 1) between mutant and wild type must be so dramatic that there is no overlap of their reaction curves, making it possible to distinguish mutant and wild-type genotypes with 100 percent certainty. In such cases, we say that this mutation is 100 percent penetrant. However, many mutations show incomplete penetrance. Penetrance is thus 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 term 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 of the allelic constitution of the rest of the genome or to environmental factors. Figure 6-18 illustrates the distinction between penetrance and expressivity. Like penetrance, expressivity is integral to the concept of the norm of reaction.

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 often is 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 6-19). 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 6-19). Similarly, variable expressivity can confound diagnosis. A specific example of variable expressivity is found in Figure 6-20.

MESSAGE
Only a subset of mutations are fully penetrant and show consistent expressivity. These experimentally reliable mutations are the most suitable for testing gene interaction patterns.

© 1999 by W. H. Freeman and Company. All rights reserved.