Detecting genetic variants is a laborious process that often involves sequencing—that is, determining the sequence of DNA building blocks (i.e., nucleotides)—for the entire gene in both affected and unaffected individuals to look for consistent differences.2 Alternatively, researchers can employ screening procedures during which they isolate small gene sections from many individuals and compare their mobility in a gelatinous material. Differences in mobility in these analyses may indicate nucleotide variations (Malhotra and Goldman 1999).3 To confirm that a potential nucleotide variation exists and to determine its exact location in the genome, investigators then must conduct additional studies, typically on the direct sequencing of the DNA section in question. This information also allows researchers to determine whether the nucleotide variation is likely to have functional significance, either because it actually results in amino acid changes in the resulting protein or because it occurs in DNA regions controlling the gene’s activity. Finally, to be useful for candidate gene studies, the variant should occur with sufficient frequency to allow detection of differences between individuals with and without the trait under investigation.
