Cystic fibrosis and phenylketonuria are both recessive diseases. This means that both copies of the gene must be defective in order for the disease to be expressed. In a person carrying a normal allele on one chromosome and its defective allele on the homologous chromosome, the presence of that one normal allele produces enough protein to provide normal function for the cell. In this case the normal phenotype is said to be dominant because the normal allele is expressed in the presence of the abnormal allele and seems to dominate it. Even though the terms dominant and recessive are strictly for describing phenotypes, they are also commonly applied to the respective causative alleles. Because one haploid "dose" of the normal allele provides enough protein to be sufficient for normal function, this general situation is termed haplo-sufficiency. Recessive alleles are given lowercase letter symbols. The three possible genotypes for a general case of haplo-sufficiency are represented in the following table, which shows dominance relations. In the table, a is the mutant (defective) allele. [In the genotypes, note the slash (/) between the allele pairs. This slash is used to designate homology in diploid organisms, and we will see extensions of its use in subsequent chapters.]

The table shows that the phenotype of a heterozygote (an individual with two different alleles for a gene) is effectively a test of dominance; if the heterozygote is normal in phenotype, then the phenotype represented by the mutant allele must be recessive. Figure 3-29 on the following page shows how this can work at the molecular level.

However, in heterozygotes for some genes, the normal allele cannot provide enough protein product to fulfill normal cell function; this situation is known as haplo-insufficiency. In these cases it is the defective (mutant) allele that is dominant. Uppercase letters are used to denote dominant mutations. As with recessive alleles, the wild-type allele is indicated by a superscript plus sign added to the letter. The general case for haplo-insufficiency can be written as follows, where B is a mutant allele:

Again we see that the test for dominance is the phenotype of the heterozygote; here the mutant phenotype (defective) is clearly dominant. There are other possible mechanisms whereby mutant alleles can express dominancefor example, by taking on new functionas we shall see in Chapters 7 and 14. These are distinguished from haplo-insufficient dominants and are called gain-of-function dominants.

A general rule of thumb is that there are many more haplo-sufficient genes than haplo-insufficient ones, but much depends on the organism and the genetic context.