The VHL gene was isolated by a strategy called positional cloning. The first step in finding the gene for VHL was to find people who had the disease. The researchers who were looking for the VHL gene contacted several types of doctors--eye doctors, urologists, and geneticists--who might be treating people with VHL. Through them, they got the names of individuals and families with the disease. Then came "linkage analysis," in which DNA markers--defined segments--on chromosome 3 were shown to be linked or not to the occurrence of the disease in each individual tested. Any marker linked to the disease was assumed to be linked physically as well to the gene that causes the disease. The researchers isolated some 2000 markers on chromosome 3, getting closer and closer to the exact location of the VHL gene. And, eventually, they isolated the VHL gene (1). Like increasingly tiny nested Russian dolls, wrote Zbar, "the nested deletions narrowed the location of the gene (8)."