POSITIONAL CLONING - A REVIEW AND PERSPECTIVE

Positional cloning has attained prominence in the biomedical field thr ough its ability to unravel the molecular basis of many elusive diseas es, including cystic fibrosis, Huntington disease, and breast cancer. The strength of positional cloning is in its ability to identify a dis ease gene without prior knowledge of the inherent biochemical defect. The process involves collection and characterization of families or po pulations of individuals segregating a disorder, localizing the defect ive gene to a chromosomal region, cloning all of the DNA, identifying all of the genes, and testing the genes for mutations that associate w ith the disease. Having identified the genetic cause of a disease, ana lysis turns toward functional elucidation. Dissection of the biochemic al pathway provides rational targets for drug discovery by providing b iologically relevant molecules for screening. (C) 1997 Wiley-Liss, Inc .