Does Phaster Mean Better?(Editorial‪)‬

The accelerated pace of discovery of disease-causing genes has made efficient mutation detection a priority. Identification of DNA sequence variants allows human geneticists to determine, among other things, whether a candidate gene contributes to disease susceptibility, to identify new alleles at known loci, and to develop molecular diagnostic tests. Once a susceptibility gene has been identified, the investigator interested in molecular diagnostics or genotype-phenotype correlation must decide how to perform rapid, sensitive detection of mutations. Grompe [1] divided these techniques into those that are most useful for identifying known mutations and those that are better for detecting novel mutations. However, he also allowed that no one method would be appropriate for all situations. Clearly, the choices investigators make will be based, in part, on what they are trying to accomplish (e.g., diagnostics vs population studies of allele frequencies); the goal will also dictate the level of sensitivity required and, conversely, the proportion of false positives or negatives that can be tolerated. Other factors such as knowledge of genomic size, sequence, and structure; availability of RNA/cDNA; and access to equipment and technical expertise will also influence the decision.