With diseases such as PKU and sickle-cell anemia, you have seen that the clinical phenotypes of inherited diseases could be traced to individual proteins, and that the genes could then be identified. For example, in sickle-cell anemia, the protein abnormality in hemoglobin was described first (a single amino acid change), and then the gene for β-globin was isolated and the DNA mutation was pinpointed.

Clinical phenotype → protein phenotype → gene

With the advent of new ways to identify DNA variations, a new pattern of human genetic analysis emerged. In these cases, the clinical phenotype is first related to a DNA variation, and then the gene and protein involved are identified. For cystic fibrosis (see Table 15.2), a mutant version of the gene CFTR was isolated first, and then the protein was characterized:

Clinical phenotype → gene → protein phenotype

Whichever approach is used, final identification of the protein(s) involved in a disease is important in designing specific therapies.