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The hybrid–inbred method has been introduced into the breeding of all kinds of plants and animals. Tomatoes and chickens, for example, are now almost exclusively hybrids. Attempts also have been made to breed hybrid wheat, but thus far the wheat hybrids obtained do not yield consistently better than do the non-hybrid varieties now used It is not possible to identify all the genes that influence the development of a given character by using purely genetic techniques. In a given population, only a subset of the genes that contribute to the development of any given character will be genetically variable. Hence, only some of the possible variation will be observed. 

This is true even for genes that determine simple qualitative traits—for example, the genes that determine the total antigenic configuration of the membrane of the human red blood cell. About 40 loci determining human blood groups are known at present; each has been discovered by finding at least one person with an immunological specificity that differs from the specificities of other people. Many other loci that determine red blood cell membrane structure may remain undiscovered because all the people studied are genetically identical. Genetic analysis detects genes only when there is some allelic variation. In contrast, molecular analysis deals directly with DNA and its translated information and so can identify genes as stretches of DNA coding for certain products, even when they do not vary—provided that the gene products can be identified.

Even though a character may show continuous phenotypic variation, the genetic basis for the differences may be allelic variation at a single locus. Most of the classic mutations in Drosophila are phenotypically variable in their expression, and in many cases, the mutant class differs little from wild type, and so many flies that carry the mutation are indistinguishable from normal flies. Even the genes of the bithorax complex, which have dramatic homeotic mutations that turn halteres into wings (see Figure 18-24), also have weak alleles that increase the size of the halteres only slightly on average, and so flies of the mutant genotype may appear to be wild type.

It is sometimes possible to use prior knowledge of the biochemistry and development of an organism to guess that variation at a known locus is responsible for at least some of the variation in a certain character. Such a locus is a candidate gene for the investigation of continuous phenotypic variation. The variation in the activity of the enzyme acid phosphatase in human red blood cells was investigated in this way. Because we are dealing with variation in enzyme activity, a good hypothesis would be that there is allelic variation at the locus that codes for this enzyme. When H. Harris and D. Hopkinson sampled an English population, they found that there were, indeed, three allelic forms, A, B, and C, that resulted in enzymes with different activity levels. 

Table 20-2 shows the mean activity, the variance inactivity, and the population frequency of the six genotypes. Figure 20-15 shows the distribution of activity for the entire population and how it is composed of the distributions of the different genotypes. As Table 20-2 shows, of the variance in activity in the total distribution (607.8), about half is explained by the average variance within genotypes (310.7); so half (607.8  310.7  297.1) must be accounted for by the variance between the means of the six genotypes. Although so much of the variation in activity is explained by the mean differences between the genotypes, there remains variation within each genotype that may be the result of environmental influences or of the segregation of other, as yet unidentified genes.