Once investigators have selected a candidate gene, they must decide which polymorphism would be most useful for testing in an association study. To this end, they must identify existing gene variants and determine which of those variants result in proteins with altered functions that might influence the trait of interest.1 (For more information on the relationship between mutations in the DNA and variations in protein function, see the sidebar, p. 167.) In the case of ALDH, several well-known polymorphisms result in the substitution of certain protein building blocks (i.e., amino acids) and thus can lead to proteins with biologically relevant changes in function. In many cases, however, researchers may know a gene’s DNA sequence but may not have any information about functional variation in the gene.
